Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Irina Vassilievna Belyaeva
 -- 3304 2022-09-14 09:31:56 |
2 Main text revised.
Lindsay Dong
+ 3 word(s) 3307 2022-09-19 08:58:58 | |
3 Reference format revised.
Lindsay Dong
Meta information modification 3307 2022-09-19 11:49:03 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Belyaeva, I.V.;  Kosova, A.N.;  Vasiliev, A.G. Tuberculosis and Autoimmunity. Encyclopedia. Available online: https://encyclopedia.pub/entry/27159 (accessed on 06 July 2024).
Belyaeva IV,  Kosova AN,  Vasiliev AG. Tuberculosis and Autoimmunity. Encyclopedia. Available at: https://encyclopedia.pub/entry/27159. Accessed July 06, 2024.
Belyaeva, Irina V., Anna N. Kosova, Andrei G. Vasiliev. "Tuberculosis and Autoimmunity" Encyclopedia, https://encyclopedia.pub/entry/27159 (accessed July 06, 2024).
Belyaeva, I.V.,  Kosova, A.N., & Vasiliev, A.G. (2022, September 14). Tuberculosis and Autoimmunity. In Encyclopedia. https://encyclopedia.pub/entry/27159
Belyaeva, Irina V., et al. "Tuberculosis and Autoimmunity." Encyclopedia. Web. 14 September, 2022.
Tuberculosis and Autoimmunity
Edit
This entry is adapted from the peer-reviewed paper 10.3390/pathophysiology29020022

It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.

tuberculosis autoimmunity cell death

1. Introduction

Tuberculosis (TB), a dangerous chronic infectious disease caused by Mycobacterium tuberculosis (Mtb), is still a threat to public health worldwide. A global total of around 10 million people became ill with TB in 2020 [1]. Drug resistance of Mtb [2], HIV infection, malnutrition, especially vitamin D deficiency, aging, autoimmune diseases, and abundant usage of immune suppressants contribute to increased incidence of TB [3].
Epidemiological studies associate microbial infections and autoimmunity (AI), hypothesizing infections to be able to trigger autoimmune diseases (AID) [4][5][6]. A number of studies have shown sera from patients with active TB to contain autoantibodies (AAB). TB has many different outcomes and complications. Autoimmunity (AI) is one of the processes characteristic of TB; at least, the presence of AABs was documented by a large amount of evidence. AABs, being typical for autoimmune disorders, are also present in different infectious diseases [5][6][7][8]. The role of AABs in the pathogenesis of TB development is widely disputed. They are considered (1) as a result of imbalanced immune response being reactive in nature [9][10][11]; (2) as a critical part of TB pathogenicity, leading to cavitation and transmission [12]; (3) as a beginning of AI disease [12][13]; (4) as a protective mechanism helping to dispose of microbes and infected cells [14]; and (5) as playing a dual role, pathogenic and protective [14]. Such diverse opinions lead to the conclusion that mechanisms involved may vary in each case. Mtb can trigger different pathways of the immune responses.
Several possible mechanisms of AI development in TB may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages (Mphs) and dendritic cells (DCs), environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mtb and host. Chronic presence of infection can be regarded as an endogenous adjuvant [15]. With the existence of different pathways of immune responses, the one receiving the support from additional factors dominates. Multiple surface Mtb molecules can differently orchestrate immune responses.

2. Occurrence of AABs in Active TB Patient Sera

Early reports have established links between Mtb and AI [7][8][16][17]. A number of studies connecting TB with AI investigated the AAB characteristics of AIDs. The list of AABs includes rheumatoid factor (RF), antinuclear antibodies (ANA), anti-dsDNA AAB, anticardiolipin antibody (ACA; IgM isotype predominant), antineutrophil cytoplasmic antibodies (ANCA), and anticyclic citrullinated peptide (anti-CCP) [8][9][11][18][19][20][21][22][23][24][25][26]. (Table 1)

Table 1. The autoantibodies in tuberculosis.
AAB Type AAB in AIDs AAB in TB
(References)
rheumatoid factor (RF) rheumatoid arthritis, Sjögren’s syndrome [7][21][24]
antinuclear antibodies (ANA) SLE, Sjögren’s syndrome, scleroderma, dermatomyositis [7][8][16][19][20][21]
anti-dsDNA antibodies SLE [10][18][19][25]
antineutrophilic cytoplasmatic antibodies (ANCA) ANCA-associated systemic vasculitis [11][22][23]
anticyclic citrullinated peptide (anti-CCP) rheumatoid arthritis [24]
anti-Scl-70, antihistone antibodies systemic sclerosis, SLE [10]
antiphospholipid antibodies (aPL): the lupus anticoagulant (LA), anticardiolipin antibody (ACA), anti-beta 2 glycoprotein 1 (anti-ß2 GPI), anti-prothrombin antiphospholipid syndrome, SLE [27][28][29]
anticardiolipin antibody (ACA; IgM) SLE, antiphospholipid syndrome [8][10][11][19]
antibodies against β2 glycoprotein IgG antiphospholipid syndrome, SLE [11]
antibodies against proteinase 3, myeloperoxidase, bactericidal/permeability-increasing protein, lactoferrin systemic vasculitis [23]
AAB—autoantibodies, AID—autoimmune disease, TB—tuberculosis, SLE—systemic lupus erythematosus.

3. The Unique Pathway of B-Cell Activation Causing IgG2a AAB Production

A similar mechanism of AAB generation for classic AIDs and microbial infections connected with the autoreactive B-cell population expressing the transcription factor T-bet has been identified [30][31][32][33]. T-bet+ B-cells were found to be major producers of AABs [31]. B cells expressing the transcription factor T-bet may take part in a number of protective and pathogenic immune responses [33]. Both in infectious and classical AI, the mechanism of activation of T-bet+ B-cells involves the recognition of a nucleic acid by toll-like receptor 7 (TLR7) and synergistic stimulation of IFNγ receptors on B cells [30][31]. These signals induce T-box transcription factor T-bet and IgG2a switching in B cells [32].
T-bet has been demonstrated to have an important role in the protective immunity against intracellular pathogens and is prone to producing AABs [33]. T-bet+ B cell induction and expansion were revealed in mouse AI models and in patients with autoimmune diseases such as SLE, MS, RA, Crohn’s disease, and Sjögren’s syndrome [31].

4. Antiphospholipid Antibodies

Antiphospholipid antibodies (aPL) were revealed in various clinical conditions (AID) and infections such as TB (summarized in [27][28][29]). The increased levels of ACA in TB patients were found in several studies [8][10][11][19]. Many viral, bacterial, and parasitic infections can induce aPL, mainly ACA, which do not correlate with thrombosis risk and antiphospholipid syndrome [27].
The elevated concentration of antibodies against β2 glycoprotein IgG and ACA IgG normalized after TB treatment was shown in active TB patients [11]. A significant number of patients had high levels of AABs against proteinase 3 (PR3), myeloperoxidase (MPO), bactericidal/permeability-increasing protein (BPI), and lactoferrin. Most antilactoferrin and anti-MPO levels decreased after treatment, while anti-PR3 increased in most patients [23]. Antiphospholipid antibody levels were suggested to use as biomarker TB treatment in noncavitary TB patients due to their high TB-treatment sensitivity [29].
Phospholipids in the Mtb cell envelope are phosphatidylglycerol, phosphatidylinositol, cardiolipin, and its mannoside derivatives, as well as phosphatidylethanolamine [34]. Because some of them can only be found in mycobacteria, they can be potential biomarkers for diagnosis and treatment response [29][35].

5. B-1 B Cells Produce IgM Antiphospholipid Antibodies, Which Have Auto- and Polyreactive Properties

Lipid molecules cause antibody response by B-1 B cells, representing about 5% of B cell population. B-1 B cells express high levels of IgM and do not need T cells for proliferation [36]. B and T cells with self-reactive antigen receptors are usually deleted during their development in order to avoid AIDs. On the contrary, innate-like B-1 cells in mice are positively selected for self-reactivity as long-lived, self-renewing B cells that generate most of the circulating natural IgM [37]. They respond to self-determinants, such as carbohydrates and glycolipids, and often cross-react with bacterial antigens. Major stimulating B-1 B cells antigens are phospholipids [36]. IgM aPL antibodies have self- and polyreactive properties [37].
The IgM antibody production by B-1 B cells needs long-term stimulation by lipid antigens generated by replicating mycobacteria during TB. Dead host cells and Mtb cells release enough antigens to activate the B-1 B cells and induce IgM aPL antibody production [29].

6. Mycobacterial Lipids Act as Adjuvants

Mycobacterial lipids have been shown to act as adjuvants. Adjuvants are a component in the vaccine stimulating innate immunity and memory-type immunity [38][39]; they are used to establish preferable types of immune responses [39].
Jules Freund created a powerful adjuvant composed of water-in-mineral oil emulsion and heat-killed mycobacteria. CFA, being highly effective, often causes granulomas, sterile abscesses, and ulcerative necrosis at the injection site and cannot be used for humans. CFA is used in experiments for modeling of AIDs such as uveitis and EAE [38]. The lipid components of CFA such as trehalose dimycolate (TDM, also known as cord factor) and mycolic-acid-containing glycolipids with strong adjuvant activity [40][41] have been shown to be a substantial factor of adjuvant activity [42]. TDM is a glycolipid in the mycobacterial cell envelope that was discovered in the 1950s as a most potent immune-stimulatory molecule [43].

7. Mycobacterium Tuberculosis–Host Cell Interaction

Central to immune response is an interaction between host professional phagocytes and Mtb, which will determine development and outcome of TB. Alveolar Mphs are the host phagocytic cells that eliminate pathogens directly or indirectly, activating the host innate and adaptive immune responses without excessive inflammation and lung destruction [44].
Multiple receptors take part in endocytosis of Mtb: they are the complement receptor [45]; the monocyte-inducible C-type lectin (Mincle), identified as the receptor for TDM (trehalose-6,6′-dimycolate) [46]; surfactant protein A (Sp-A) and its receptors [47][48][49]; scavenger receptor [50]; mannose receptors [50][51]; and the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN, CD209) [52][53]. DC-SIGN interactions with Mtb may be of benefit for either the pathogen or for the host due to restriction of tissue inflammation and immunopathology [54][55][56]. DC-SIGN is expressed on both wound-healing (IL-4-dependent) and regulatory (M-CSF-dependent) alternative (M2) macrophages [56]. Pattern-recognition receptors also respond to Mtb, among them the TLR-1, TLR-2, TLR-4, TLR-6, TLR7, and TLR-9 on Mphs and DCs, thereby driving phagocytosis, antigen presentation to T cells, and cytokine secretion [57][58][59].
Polymorphisms in TLRs affect human susceptibility to tuberculosis [60][61] and possibly to AI.

8. Unique Protein Family PE/PPE/PGRS Present on the Mtb Surface

Some molecules present on the Mtb surface are unique. The genome of Mtb encodes a protein family PE/PPE/PGRS, present exclusively in the genus Mycobacterium [62]. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined in 1998 by Cole et al. and a family of genes, the Proline–Glutamic acid/Proline–Proline–Glutamic acid (PE/PPE), has been identified [63]. These genes are principally characteristic of the pathogenic strains. The data on this important family of proteins are summarized in the paper [64].
PE proteins are divided in three subfamilies: PE; PE/PPE; and PE_PGRS containing the polymorphic glycine-rich domain of variable sequence and size [64].
PE/PPE proteins have been reported to use the host inflammatory signaling and cell-death pathways to facilitate disease development [65]. It is widely recognized that PE_PGRS [polymorphic GC-rich-sequence (PGRS)] proteins are essential in TB pathogenesis [64][66][67].

9. Mycobacterium tuberculosis Manipulates the Host Immune Response

The data showing that multiple molecules on the Mtb surface promote phagocytosis suggest that Mtb finds the intracellular environment of macrophages especially advantageous for surviving [68][69]. Mycobacteria manipulate host phagocytes to survive and replicate in these cells. PE_PGRS30 protein of Mtb blocks phagosome maturation [70]. Autophagy, a potent host defense mechanism, is impaired by several Mtb mechanisms [70][71][72][73][74]. PE_PGRS11 can induce maturation and activation of human DCs, which promotes the secretion of proinflammatory cytokines [75]. PE_PGRS17 binding to TLR2 activates the NF-κB signaling pathway, inducing TNF-α secretion [75].
Hyperactive immune response leads to robust inflammation, which induces dissemination and transmission of bacteria and possibly AI development.

10. PE_PGRS Proteins in TB Pathogenesis

Studies of pe_pgrs genes demonstrated that expression levels of different pe_pgrs genes could differ essentially [64], leading to a diverse picture and different outcome of TB. Each protein of the PE_PGRS family can fulfill its unique function without a specific protein partner. The identification of PE_PGRS proteins in Mtb and understanding their functions leads to the acknowledgement of their potent role in the TB pathogenesis [64]. It is possible to suggest the involvement of PE_PGRS proteins in AI promotion.

11. Excessive Cell Death as a Possible Mechanism of Autoimmunity

Cell death is a substantial physiological and pathological process involved in coordination of immune responses and AI [76]. Normally after cells die they are quickly and smoothly removed by phagocytes without inflammation [77][78]. However, during chronic infection, a large number of cells die, releasing massive amounts of cellular contents into the extracellular space. Released molecules are known as danger-associated molecular patterns (DAMPs) acting as damage signals, which attract additional immune cells to clear the threat and promote tissue repair [76].
Apoptosis is immunologically silent cell elimination without inducing inflammation due to containing the distracted contents of dying cells within membrane-bound vesicles called apoptotic bodies [77][79]. Many cellular signals can lead to cell death in a controlled manner [80]. The morphological changes during apoptosis are cytoskeletal disruption, cell shrinkage, DNA fragmentation, and plasma membrane blebbing [81]. Many nuclear autoantigens have been shown to accumulate within apoptotic blebs [82][83]. It was shown that apoptotic vesicles from Mtb-infected macrophages had potent adjuvant effects, stimulating CD8 T cells in vivo [84].
Apoptotic bodies are engulfed later by another phagocyte in a process termed efferocytosis [85][86]. ACs release “find me” signals such as soluble lysophosphatidylcholine, CXC3CL1, sphingosine-1-phosphate, ATP, and UTP that attract phagocytes for the clearance of apoptotic bodies [87]. It was shown that in TB, such a role plays CX3CL1 and its receptor CX3CR1 [88]. The best-studied signal “eat me” is an oxidized phosphatidylserine and oxidized low-density lipoprotein on the surface of the phagocyte [87][89]. Phosphatidylserine, a membrane component of ACs, plays an important role in the clearance of apoptotic bodies by the efferocytosis process [85][90].

12. Defective Dead Cell Clearance in Etiopathogenesis of Autoimmune Diseases

Infections have been shown to be linked with the onset of SLE [4][5]. The potential connection between infections and AI could be clearance deficiency [4]. Apoptotic cells are frequently not cleared adequately in SLE [91][92][93][94][95]; as a result, autoantigens are presented to B cells by follicular DCs in secondary lymphoid tissues [92][93][96]. Nucleic acids and the proteins binding to nucleic acids are the main autoantigens in the AID SLE [97]. Nuclear and membrane autoantigens accumulate in lymphoid organs and is thought to activate the autoreactive B and T cells, causing the production of antinuclear and antiphospholipoprotein AABs [96]. The production of antinuclear AABs and binding them to apoptotic nuclear remnants leads to chronic tissue damage, and development of systemic AIDs [93].

13. Modulation of Cell-Death Pathways by Mycobacterium tuberculosis

Among the various cell-death types in TB were documented apoptosis, pyroptosis, autophagy, and necrosis [98]. Impairment of apoptosis and autophagy provides a survival niche to Mtb [69][99]. Mycobacteria can modulate the death of the host cells. The popular opinion is that virulent Mtb inhibits apoptosis, while avirulent mycobacteria stimulate it. Virulent strains H37Rv and GC1237 are the most effective inhibitors of experimentally induced cell death. However opposite data from different experimental systems evidence that cell death results from complex interrelations of pro- and anticytotoxic mechanisms [100]. RipA, a secretory peptidoglycan hydrolase, damages both autophagy and apoptosis in Mph for intracellular survival and virulence [74].

14. MerTK Is a Major Macrophage Apoptotic-Cell Receptor

MerTK is expressed in primary and secondary lymphoid organs and is responsible for both central and peripheral tolerance through multiple mechanisms: clearance of AC-derived potential autoantigens [101]; reduction of proinflammatory cytokines production [102]; prevention of autoreactive B- and T-cell expansion [103][104]. In SLE patients, diminished AC removal is believed to promote the production of AABs against apoptotic material [86][95]. These patients had reduced plasma levels of the MerTK ligand Protein S [105], which may explain functionally defective AC clearance [106].
Populations of phagocytes M2c (CD163+) Mphs remove ACs, including apoptotic immune cells in healthy individuals, and release anti-inflammatory cytokines [107]. M-CSF was found to differentiate Mphs in the presence of IL-10, which express high levels of MerTK; such Mphs have M2c phenotypes. Gene polymorphisms of MerTK and its ligand growth arrest-specific 6 (Gas6) are connected with clinical manifestations in SLE patients [108][109].

15. Macrophage Polarization Programs

Mature Mphs can undergo functional polarization in response to environmental signals. Two well-appreciated Mph polarization programs are (M1) induced by LPS+IFNγ, secreting IL-12 and promoting Th1 differentiation; (M2) Mphs that are induced by IL-4: (M2a), secreting IL-4 and inducing Th2 polarization; (M2b) and (M2c), both secreting IL-10 and linked with regulatory T-cell (Treg) propagation [110]. These cells can switch from one phenotype to another. They can either facilitate a proinflammatory or an anti-inflammatory effect, which makes them a potential participant in the development of AIDs [111].

16. Immune Tolerance

DCs present self-antigens to developing T cells in thymus and delete lymphocytes with autoreactivity [112]. Central tolerance control occurring in thymus through mechanism of selection leads to release into the circulation of high-affinity T cells specific for non-self-antigens, low-affinity T cells specific for self-antigens, and natural Treg (nTreg) with an intermediate affinity to both self- and non-self-antigens [113].

Two types of peripheral tolerance mechanism exist in a steady state after antigen capture by DCs [114]. One is the T-cell deletion involving activation of the programmed death 1 (PD-1) and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) on T cells [115]. Immune checkpoints CTLA-4 and PD-1 are negative regulators of T-cell immune function. A second is the induction of foxp3+ regulatory T cells (Tregs) [116][117][118]. Fms-like tyrosine kinase 3 ligand (flt-3L) is a hematopoietin necessary for expanding DC subsets and Tregs in vivo [119]. The use of flt-3L has been shown to be effective in treating AI in mice [119][120][121].

17. Dendritic Cell Subsets

Several DC subsets have been identified by their ontogeny, phenotype, and transcriptional profile [122]. In humans, blood DCs are defined as CD303+, CD304+, CD123+, plasmacytoid DCs, and conventional DCs (cDCs), the latter divided into two subsets, the CD1c+ DCs and the CD141+ DCs [123]. More recently, a third subset of DCs, named monocyte-derived DCs (Mo-DCs), has been described in patients with RA and in other inflammatory states [124][125][126]. These cells differentiate from monocytes in inflamed tissues and induce Th1, Th17, or Th2 responses depending on the signal received [127].

The plasticity of DCs, dependent on different extents of maturity, may be used in cell-based therapy to restore immune tolerance in AIDs. The beneficial effect of tolerogenic DC (tolDC) has been demonstrated in autoimmune models in mice. They caused immune tolerance, resolution of immune responses and prevention of AI by inhibition of effector and autoreactive T cells and by promotion of Treg cells [128][129][130]. TolDCs have become promising cell-based therapies for treatment of AIDs [131][132][133][134][135].

18. Vitamin D, Autoimmunity, Tuberculosis

Vitamin D has been discovered to have an important immune-modulatory function, enhancing the innate and inhibiting the adaptive immune response and acting as an environmental factor facilitating AID development [136][137][138][139][140][141][142][143][144][145]. The optimal vitamin D concentration beneficial for health and preventing the risk of AIDs was declared to be 30–40 ng/mL 25(OH)D [146].

Vitamin D inhibits the maturation and antigen presentation of DCs [141][147] and changes the profile of T-helper cells (Th1, Th2, Th9, Th17) and Treg cells [148]. It was reported that vitamin D lowers Th1 cell function, leading to decreased production of TNF-alpha, IL-2, granulocyte macrophage colony-stimulating factor (GMCSF) and IFN-gamma [149][150]. However, vitamin D increases the differentiation and proliferation of Th2 and Treg cells, which in turn stimulates the production of their anti-inflammatory cytokines IL-4, IL-5, and IL-10, which further suppress the development of Th1, Th17, and Th9 cells, producing immune tolerance [151]. 

High titers of various AABs present in pulmonary TB patients with vitamin D deficiency [18][19][152][153]. It revealed calcitriol deficiency and lack of proper cathelicidin response to infection in various forms of TB [18]. At the same time, these TB patients were characteristic of increased production of Th1 and Th17-derived cytokines and had blood prolactin level increased, which is well-known stimulator of AI [154]. These features taken together could be responsible for a greater inclination of TB patients to AI, and patients actually demonstrated increased levels of AABs towards several antigens, especially in more severe fibrous-cavernous forms of TB [18].

19. Th Cells and Cytokines in Tuberculosis

Th1 and Th17 are the main effector cells mediating protection and pathology during TB. Th1 cells have been established to facilitate protective action by secreting IFN-γ and activating Mphs. IFNγ has long been known as a regulator of T-cell responses in mycobacterial disease contributing to the elimination of mycobacteria-infected cells [155].
The function of Th17 cells during TB infection is complex because the pathogenesis of TB largely depends on the gravity of inflammation. Multiple data on Th17 actions in TB received both on mouse models and clinical TB show different results. Th17 induces chemokine and cytokine production, leading to neutrophil recruitment, tissue damage, and inflammation [155]. It was suggested that IL-17 may be protective during acute infection and detrimental during chronic ones [156] and in multidrug-resistant TB [157].
Heterogeneous cell populations Th1 and Th17 include subpopulations with diverse cytokine profiles playing different roles in immune pathology and protection. Th17.1 produces IFN-γ/TNF-α and IL-17 differentiating from Th17 in the presence of IL-12 and inflammatory cytokines, primarily IL-1β [155]. Th17.1 cells were found to be extremely pathogenic in the course of AIDs, but the role for these cells in active TB remains unclear. Th17.1 cells were detected in the broncho-alveolar fluid and lungs TB patients [155].

References

  1. WHO. Global Tuberculosis Report 2021; WHO: Geneva, Switzerland, 2021.
  2. Allué-Guardia, A.; García, J.I.; Torrelles, J.B. Evolution of Drug-Resistant Mycobacterium tuberculosis Strains and Their Adaptation to the Human Lung Environment. Front. Microbiol. 2021, 12, 612675.
  3. Lyadova, I.; Nikitina, I. Cell Differentiation Degree as a Factor Determining the Role for Different T-Helper Populations in Tuberculosis Protection. Front. Immunol. 2019, 10, 972.
  4. Schulze, C.; Munoz, L.; Franz, S.; Sarter, K.; Chaurio, R.; Gaipl, U.; Herrmann, M. Clearance deficiency—A potential link between infections and autoimmunity. Autoimmun. Rev. 2008, 8, 5–8.
  5. Esposito, S.; Bosis, S.; Semino, M.; Rigante, D. Infections and systemic lupus erythematosus. Eur. J. Clin. Microbiol. 2014, 33, 1467–1475.
  6. Rigante, D.; Esposito, S. Infections and Systemic Lupus Erythematosus: Binding or Sparring Partners? Int. J. Mol. Sci. 2015, 16, 17331–17343.
  7. Isenberg, D.A.; Maddison, P.; Swana, G.; Skinner, R.P.; Swana, M.; Jones, M.; Addison, I.; Dudeney, C.; Shall, S.; Roiey, A.E.; et al. Profile of autoantibodies in the serum of patients with tuberculosis, klebsiella and other Gram-negative infections. Clin. Exp. Immunol. 1987, 67, 516–523.
  8. Adebajo, A.O.; Charles, P.; Maini, R.N.; Hazleman, B.L. Autoantibodies in malaria, tuberculosis and hepatitis B in a West African population. Clin. Exp. Immunol. 1993, 92, 73–76.
  9. Franco-Paredes, C.; Díaz-Borjon, A.; Senger, M.A.; Barragan, L.; Leonard, M. The Ever-Expanding Association Between Rheumatologic Diseases and Tuberculosis. Am. J. Med. 2006, 119, 470–477.
  10. Shen, C.-Y.; Hsieh, S.-C.; Yu, C.-L.; Wang, J.-Y.; Lee, L.-N.; Yu, C.-J. Autoantibody prevalence in active tuberculosis: Reactive or pathognomonic? BMJ Open 2013, 3, e002665.
  11. Elkayam, O.; Bendayan, D.; Segal, R.; Shapira, Y.; Gilburd, B.; Reuter, S.; Agmon-Levin, N.; Shoenfeld, Y. The effect of anti-tuberculosis treatment on levels of anti-phospholipid and anti-neutrophil cytoplasmatic antibodies in patients with active tuberculosis. Rheumatol. Int. 2012, 33, 949–953.
  12. Elkington, P.; Tebruegge, M.; Mansour, S. Tuberculosis: An Infection-Initiated Autoimmune Disease? Trends Immunol. 2016, 37, 815–818.
  13. Chen, S.; Chen, J.; Chen, L.; Zhang, Q.; Luo, X.; Zhang, W. Mycobacterium tuberculosis Infection Is Associated with the Development of Erythema Nodosum and Nodular Vasculitis. PLoS ONE 2013, 8, e62653.
  14. Rivera-Correa, J.; Rodriguez, A. Divergent Roles of Antiself Antibodies during Infection. Trends Immunol. 2018, 39, 515–522.
  15. Shapira, Y.; Agmon-Levin, N.; Shoenfeld, Y. Mycobacterium tuberculosis, Autoimmunity, and Vitamin D. Clin. Rev. Allergy Immunol. 2009, 38, 169–177.
  16. Rapoport, B.L.; Morrison, R.C.; Sher, R.; Dos Santos, L. A study of autoantibodies in chronic mycobacterial infections. Int. J. Lepr. Other Mycobact. Dis. 1990, 58, 518–525.
  17. Lindqvist, K.J.; Coleman, R.E.; Osterland, C. Autoantibodies in chronic pulmonary tuberculosis. J. Chronic Dis. 1970, 22, 717–725.
  18. Belyaeva, I.V.; Churilov, L.P.; Mikhailova, L.R.; Nikolaev, A.V.; Starshinova, A.A.; Yablonsky, P.K. Vitamin D, Cathelicidin, Prolactin, Autoantibodies, and Cytokines in Different Forms of Pulmonary Tuberculosis versus Sarcoidosis. IMAJ 2017, 19, 499–505.
  19. Elkayam, O.; Caspi, D.; Lidgi, M.; Segal, R. Auto-antibody profiles in patients with active pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 2007, 11, 306–310.
  20. Ganesh, R.; Ramalingam, V.; Raja, T.E.; Vasanthi, T. Antinuclear antibodies in Mycobacterium tuberculosis infection. Indian J. Pediatr. 2008, 75, 1188.
  21. Kasikovic-Lecic, S.; Kerenji, A.; Pavlovic, S.; Kuruc, V.; Mitic, I.; Ilic, T. Autoantibodies in patients treated for active pulmonary tuberculosis. Med. Rev. 2008, 61, 333–342.
  22. Flores-Suárez, L.F.; Cabiedes, J.; Villa, A.R.; Van Der Woude, F.J.; Alcocer-Varela, J. Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis. Rheumatology 2003, 42, 223–229.
  23. Esquivel-Valerio, J.; Flores-Suárez, L.F.; Rodríguez-Amado, J.; Garza-Elizondo, M.A.; Rendon, A.; Salinas-Carmona, M.C. Antineutrophil cytoplasm autoantibodies in patients with tuberculosis are directed against bactericidal/permeability increasing protein and are detected after treatment initiation. Clin. Exp. Rheumatol. 2010, 28, S35.
  24. Elkayam, O.; Segal, R.; Lidgi, M.; Caspi, D. Positive anti-cyclic citrullinated proteins and rheumatoid factor during active lung tuberculosis. Ann. Rheum. Dis. 2006, 65, 1110–1112.
  25. Shahzad, F.; Ali, A.; Mushtaq, A.; Javaid, K.; Nazir, A.; Pervez, A.; Kashif, M.; Bashir, N.; Abbas, A.; Tahir, R.; et al. Raised dsDNA autoantibodies in tuberculosis patients. Egypt. J. Chest Dis. Tuberc. 2019, 68, 28–31.
  26. Cheng, M.P.; Butler-Laporte, G.; Parkes, L.O.; Bold, T.D.; Fritzler, M.J.; Behr, M.A. Prevalence of Auto-Antibodies in Pulmonary Tuberculosis. Open Forum Infect. Dis. 2019, 6, ofz114.
  27. Sène, D.; Piette, J.-C.; Cacoub, P. Antiphospholipid antibodies, antiphospholipid syndrome and infections. Autoimmun. Rev. 2008, 7, 272–277.
  28. Martirosyan, A.; Aminov, R.; Manukyan, G. Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation. Front. Immunol. 2019, 10, 1609.
  29. Goodridge, A.; Cueva, C.; Lahiff, M.; Muzanye, G.; Johnson, J.L.; Nahid, P.; Riley, L.W. Anti-phospholipid antibody levels as biomarker for monitoring tuberculosis treatment response. Tuberculosis 2012, 92, 243–247.
  30. Rubtsova, K.; Rubtsov, A.V.; van Dyk, L.F.; Kappler, J.W.; Marrack, P. T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance. Proc. Natl. Acad. Sci. USA 2013, 110, E3216–E3224.
  31. Rubtsov, A.V.; Marrack, P.; Rubtsova, K. T-bet expressing B cells—Novel target for autoimmune therapies? Cell. Immunol. 2017, 321, 35–39.
  32. Knox, J.J.; Myles, A.; Cancro, M.P. T-bet+ B cells: Generation, function, and fate. Immunol. Rev. 2019, 288, 149–160.
  33. Rubtsov, A.V.; Rubtsova, K.; Fischer, A.; Meehan, R.T.; Gillis, J.Z.; Kappler, J.W.; Marrack, P. Toll-like receptor 7 (TLR7)–driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity. Blood 2011, 118, 1305–1315.
  34. Brennan, P.J.; Nikaido, H. The envelope of mycobacteria. Annu. Rev. Biochem. 1995, 64, 29–63.
  35. Takenami, I.; de Oliveira, C.C.; Petrilli, J.D.; Machado, A.; Riley, L.W.; Arruda, S. Serum antiphospholipid antibody levels as biomarkers for diagnosis of pulmonary tuberculosis patients. Int. J. Tuberc. Lung Dis. 2018, 22, 1063–1070.
  36. Hardy, R.R. B-1 B Cell Development. J. Immunol. 2006, 177, 2749–2754.
  37. Baumgarth, N. The double life of a B-1 cell: Self-reactivity selects for protective effector functions. Nat. Rev. Immunol. 2010, 11, 34–46.
  38. Apostolico, J.D.S.; Lunardelli, V.A.; Coirada, F.C.; Boscardin, S.B.; Rosa, D.S. Adjuvants: Classification, modus operandi, and licensing. J. Immunol. Res. 2016, 2016, 1459394.
  39. Coffman, R.L.; Sher, A.; Seder, R.A. Vaccine Adjuvants: Putting Innate Immunity to Work. Immunity 2010, 33, 492–503.
  40. Decout, A.; Silva-Gomes, S.; Drocourt, D.; Barbe, S.; André, I.; Cueto, F.J.; Lioux, T.; Sancho, D.; Pérouzel, E.; Vercellone, A.; et al. Rational design of adjuvants targeting the C-type lectin Mincle. Proc. Natl. Acad. Sci. USA 2017, 114, 2675–2680.
  41. Ishikawa, E.; Mori, D.; Yamasaki, S. Recognition of Mycobacterial Lipids by Immune Receptors. Trends Immunol. 2017, 38, 66–76.
  42. Billiau, A.; Matthys, P. Modes of action of Freund’s adjuvants in experimental models of autoimmune diseases. J. Leukoc. Biol. 2001, 70, 849–860.
  43. Noll, H.; Bloch, H.; Asselineau, J.; Lederer, E. The chemical structure of the cord factor of Mycobacterium tuberculosis. Biochim. Biophys. Acta 1956, 20, 299–309.
  44. Evren, E.; Ringqvist, E.; Willinger, T. Origin and ontogeny of lung macrophages: From mice to humans. Immunology 2020, 160, 126–138.
  45. Schlesinger, L.S.; Bellinger-Kawahara, C.G.; Payne, N.R.; Horwitz, M.A. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J. Immunol. 1990, 144, 2771–2780.
  46. Ishikawa, E.; Mori, D.; Yamasaki, S. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J. Exp. Med. 2009, 206, 2879–2888.
  47. Schlesinger, L.S.; Torrelles, J.B.; Azad, A.K.; Henning, L.N.; Carlson, T.K. Role of C-type lectins in mycobacterial infections. Curr. Drug Targets 2008, 9, 102–112.
  48. Torrelles, J.B.; Schlesinger, L.S. Integrating Lung Physiology, Immunology, and Tuberculosis. Trends Microbiol. 2017, 25, 688–697.
  49. Garcia-Vilanova, A.; Chan, J.; Torrelles, J.B. Underestimated Manipulative Roles of Mycobacterium tuberculosis Cell Envelope Glycolipids During Infection. Front. Immunol. 2019, 10, 2909.
  50. Ernst, J.D. Macrophage Receptors for Mycobacterium tuberculosis. Infect. Immun. 1998, 66, 1277–1281.
  51. Rajaram, M.V.; Arnett, E.; Azad, A.K.; Guirado, E.; Ni, B.; Gerberick, A.D.; He, L.-Z.; Keler, T.; Thomas, L.J.; Lafuse, W.; et al. M. tuberculosis -Initiated Human Mannose Receptor Signaling Regulates Macrophage Recognition and Vesicle Trafficking by FcRγ-Chain, Grb2, and SHP-1. Cell Rep. 2017, 21, 126–140.
  52. Lugo, G.; Troegeler, A.; Balboa, L.; Lastrucci, C.; Duval, C.; Mercier, I.; Bénard, A.; Capilla, F.; Al Saati, T.; Poincloux, R.; et al. The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis. Front. Immunol. 2018, 9, 1123.
  53. Tailleux, L.; Schwartz, O.; Herrmann, J.-L.; Pivert, E.; Jackson, M.; Amara, A.; Legres, L.; Dreher, D.; Nicod, L.P.; Gluckman, J.C.; et al. DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells. J. Exp. Med. 2002, 197, 121–127.
  54. Tailleux, L.; Pham-Thi, N.; Bergeron-Lafaurie, A.; Herrmann, J.-L.; Charles, P.; Schwartz, O.; Scheinmann, P.; Lagrange, P.H.; De Blic, J.; Tazi, A.; et al. DC-SIGN Induction in Alveolar Macrophages Defines Privileged Target Host Cells for Mycobacteria in Patients with Tuberculosis. PLOS Med. 2005, 2, e381.
  55. Tailleux, L.; Gicquel, B.; Neyrolles, O. Mycobacterium tuberculosis and Dendritic Cells: Whos Manipulating Whom? Curr. Immunol. Rev. 2005, 1, 101–105.
  56. Domínguez-Soto, A.; Sierra-Filardi, E.; Puig-Kröger, A.; Pérez-Maceda, B.; Gómez-Aguado, F.; Corcuera, M.T.; Sánchez-Mateos, P.; Corbí, A.L. Dendritic Cell-Specific ICAM-3–Grabbing Nonintegrin Expression on M2-Polarized and Tumor-Associated Macrophages Is Macrophage-CSF Dependent and Enhanced by Tumor-Derived IL-6 and IL-10. J. Immunol. 2011, 186, 2192–2200.
  57. Ryffel, B.; Fremond, C.; Jacobs, M.; Parida, S.K.; Botha, T.; Schnyder, B.; Quesniaux, V. Innate immunity to mycobacterial infection in mice: Critical role for toll-like receptors. Tuberculosis 2005, 85, 395–405.
  58. Faridgohar, M.; Nikoueinejad, H. New findings of Toll-like receptors involved in Mycobacterium tuberculosis infection. Pathog. Glob. Health 2017, 111, 256–264.
  59. Tsolaki, A.G.; Varghese, P.M.; Kishore, U. Innate Immune Pattern Recognition Receptors of Mycobacterium tuberculosis: Nature and Consequences for Pathogenesis of Tuberculosis. Adv. Exp. Med. Biol. 2021, 1313, 179–215.
  60. Ma, X.; Liu, Y.; Gowen, B.B.; Graviss, E.A.; Clark, A.G.; Musser, J.M. Full-Exon Resequencing Reveals Toll-Like Receptor Variants Contribute to Human Susceptibility to Tuberculosis Disease. PLoS ONE 2007, 2, e1318.
  61. Velez, D.R.; Wejse, C.; Stryjewski, M.E.; Abbate, E.; Hulme, W.F.; Myers, J.L.; Estevan, R.; Patillo, S.G.; Olesen, R.; Tacconelli, A.; et al. Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. Qual. Life Res. 2010, 127, 65–73.
  62. Grover, S.; Sharma, T.; Singh, Y.; Kohli, S.; Singh, A.; Semmler, T.; Wieler, L.H.; Tedin, K.; Ehtesham, N.Z.; Hasnain, S.E. The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4. mBio 2018, 9, e01017-18.
  63. Cole, S.T.; Brosch, R.; Parkhill, J.; Garnier, T.; Churcher, C.; Harris, D.; Gordon, S.V.; Eiglmeier, K.; Gas, S.; Barry, C.E., 3rd; et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998, 393, 537–544.
  64. De Maio, F.; Berisio, R.; Manganelli, R.; Delogu, G. PE_PGRS proteins of Mycobacterium tuberculosis: A specialized molecular task force at the forefront of host–pathogen interaction. Virulence 2020, 11, 898–915.
  65. Sharma, N.; Shariq, M.; Quadir, N.; Singh, J.; Sheikh, J.A.; Hasnain, S.E.; Ehtesham, N.Z. Mycobacterium tuberculosis Protein PE6 (Rv0335c), a Novel TLR4 Agonist, Evokes an Inflammatory Response and Modulates the Cell Death Pathways in Macrophages to Enhance Intracellular Survival. Front. Immunol. 2021, 12, 696491.
  66. Delogu, G.; Pusceddu, C.; Bua, A.; Fadda, G.; Brennan, M.J.; Zanetti, S. Rv1818c-encoded PE_PGRS protein of Mycobacterium tuberculosis is surface exposed and influences bacterial cell structure. Mol. Microbiol. 2004, 52, 725–733.
  67. Camassa, S.; Palucci, I.; Iantomasi, R.; Cubeddu, T.; Minerva, M.; De Maio, F.; Jouny, S.; Petruccioli, E.; Goletti, D.; Ria, F.; et al. Impact of pe_pgrs33 Gene Polymorphisms on Mycobacterium tuberculosis Infection and Pathogenesis. Front. Cell. Infect. Microbiol. 2017, 7, 137.
  68. Price, J.V.; Vance, R.E. The Macrophage Paradox. Immunity 2014, 41, 685–693.
  69. Mitchell, G.; Chen, C.; Portnoy, D.A. Strategies Used by Bacteria to Grow in Macrophages. Microbiol. Spectr. 2016, 4, 701–725.
  70. Thi, E.P.; Hong, C.J.H.; Sanghera, G.; Reiner, N.E. Identification of the Mycobacterium tuberculosis protein PE-PGRS62 as a novel effector that functions to block phagosome maturation and inhibit iNOS expression. Cell. Microbiol. 2012, 15, 795–808.
  71. Shin, D.-M.; Jeon, B.-Y.; Lee, H.-M.; Jin, H.S.; Yuk, J.-M.; Song, C.-H.; Lee, S.-H.; Lee, Z.-W.; Cho, S.-N.; Kim, J.M.; et al. Mycobacterium tuberculosis Eis Regulates Autophagy, Inflammation, and Cell Death through Redox-dependent Signaling. PLOS Pathog. 2010, 6, e1001230.
  72. Saini, N.K.; Baena, A.; Ng, T.; Venkataswamy, M.M.; Kennedy, S.C.; Kunnath-Velayudhan, S.; Carreño, L.J.; Xu, J.; Chan, J.; Larsen, M.H.; et al. Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47. Nat. Microbiol. 2016, 1, 16133.
  73. Shariq, M.; Quadir, N.; Sheikh, J.A.; Singh, A.K.; Bishai, W.R.; Ehtesham, N.Z.; Hasnain, S.E. Post translational modifications in tuberculosis: Ubiquitination paradox. Autophagy 2021, 17, 814–817.
  74. Shariq, M.; Quadir, N.; Sharma, N.; Singh, J.; Sheikh, J.A.; Khubaib, M.; Hasnain, S.E.; Ehtesham, N.Z. Mycobacterium tuberculosis RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation. Front. Immunol. 2021, 12, 636644.
  75. Bansal, K.; Elluru, S.R.; Narayana, Y.; Chaturvedi, R.; Patil, S.A.; Kaveri, S.V.; Bayry, J.; Balaji, K.N. PE_PGRS Antigens of Mycobacterium tuberculosis Induce Maturation and Activation of Human Dendritic Cells. J. Immunol. 2010, 184, 3495–3504.
  76. Bertheloot, D.; Latz, E.; Franklin, B.S. Necroptosis, pyroptosis and apoptosis: An intricate game of cell death. Cell. Mol. Immunol. 2021, 18, 1106–1121.
  77. Strasser, A.; O’Connor, L.; Dixit, V.M. Apoptosis Signaling. Annu. Rev. Biochem. 2000, 69, 217–245.
  78. Fink, S.L.; Cookson, B.T. Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells. Infect. Immun. 2005, 73, 1907–1916.
  79. Tiwari, B.; Ramakrishnan, U.M.; Raghunand, T.R. The Mycobacterium tuberculosis protein pair PE9 (Rv1088)-PE10 (Rv1089) forms heterodimers and induces macrophage apoptosis through Toll-like receptor 4. Cell. Microbiol. 2015, 17, 1653–1669.
  80. Epieterse, E.; Der Vlag, J.E. Breaking Immunological Tolerance in Systemic Lupus Erythematosus. Front. Immunol. 2014, 5, 164.
  81. Saraste, A.; Pulkki, K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc. Res. 2000, 45, 528–537.
  82. Rosen, A.; Casciola-Rosen, L.; Ahearn, J. Novel packages of viral and self-antigens are generated during apoptosis. J. Exp. Med. 1995, 181, 1557–1561.
  83. Brinkmann, V.; Reichard, U.; Goosmann, C.; Fauler, B.; Uhlemann, Y.; Weiss, D.S.; Weinrauch, Y.; Zychlinsky, A. Neutrophil extracellular traps kill bacteria. Science 2004, 303, 1532–1535.
  84. Winau, F.; Weber, S.; Sad, S.; de Diego, J.; Hoops, S.L.; Breiden, B.; Sandhoff, K.; Brinkmann, V.; Kaufmann, S.H.; Schaible, U.E. Apoptotic Vesicles Crossprime CD8 T Cells and Protect against Tuberculosis. Immunity 2006, 24, 105–117.
  85. Henson, P.M. Cell Removal: Efferocytosis. Annu. Rev. Cell Dev. Biol. 2017, 33, 127–144.
  86. Muñoz, L.E.; Janko, C.; Grossmayer, G.E.; Frey, B.; Voll, R.E.; Kern, P.; Kalden, J.R.; Schett, G.; Fietkau, R.; Herrmann, M.; et al. Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus. Arthritis Care Res. 2009, 60, 1733–1742.
  87. Hochreiter-Hufford, A.; Ravichandran, K. Clearing the Dead: Apoptotic Cell Sensing, Recognition, Engulfment, and Digestion. Cold Spring Harb. Perspect. Biol. 2013, 5, a008748.
  88. Hingley-Wilson, S.M.; Connell, D.; Pollock, K.; Hsu, T.; Tchilian, E.; Sykes, A.; Grass, L.; Potiphar, L.; Bremang, S.; Kon, O.M.; et al. ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans. Tuberculosis 2014, 94, 262–270.
  89. Gardai, S.J.; Bratton, N.L.; Ogden, C.A.; Henson, P.M. Recognition ligands on apoptotic cells: A perspective. J. Leukoc. Biol. 2006, 79, 896–903.
  90. Birge, R.B.; Boeltz, S.; Kumar, S.; Carlson, J.; Wanderley, J.; Calianese, D.; Barcinski, M.; Brekken, R.A.; Huang, X.; Hutchins, J.T.; et al. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death Differ. 2016, 23, 962–978.
  91. Munoz, L.E.; Gaipl, U.S.; Franz, S.; Sheriff, A.; Voll, R.E.; Kalden, J.R.; Herrmann, M. SLE—A disease of clearance deficiency? Rheumatology 2005, 44, 1101–1107.
  92. Muñoz, L.E.; Janko, C.; Schulze, C.; Schorn, C.; Sarter, K.; Schett, G.; Herrmann, M. Autoimmunity and chronic inflammation—Two clearance-related steps in the etiopathogenesis of SLE. Autoimmun. Rev. 2010, 10, 38–42.
  93. Mahajan, A.; Herrmann, M.; Muñoz, L.E. Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE. Front. Immunol. 2016, 7, 35.
  94. Kuhn, A.; Herrmann, M.; Kleber, S.; Beckmann-Welle, M.; Fehsel, K.; Martin-Villalba, A.; Lehmann, P.; Ruzicka, T.; Krammer, P.H.; Kolb-Bachofen, V. Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation. Arthritis Care Res. 2006, 54, 939–950.
  95. Munoz, L.; Lauber, K.; Schiller, M.; Manfredi, A.A.; Herrmann, M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat. Rev. Rheumatol. 2010, 6, 280–289.
  96. Baumann, I.; Kolowos, W.; Voll, R.E.; Manger, B.; Gaipl, U.; Neuhuber, W.L.; Kirchner, T.; Kalden, J.R.; Herrmann, M. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Care Res. 2002, 46, 191–201.
  97. Qiu, C.; Caricchio, R.; Gallucci, S. Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens. Front. Immunol. 2019, 10, 2608.
  98. Parandhaman, D.K.; Enarayanan, S. Cell death paradigms in the pathogenesis of Mycobacterium tuberculosis infection. Front. Cell. Infect. Microbiol. 2014, 4, 31.
  99. Cohen, S.B.; Gern, B.; Delahaye, J.L.; Adams, K.N.; Plumlee, C.R.; Winkler, J.K.; Sherman, D.R.; Gerner, M.Y.; Urdahl, K.B. Alveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination. Cell Host Microbe 2018, 24, 439–446.e4.
  100. Butler, R.E.; Brodin, P.; Jang, J.; Jang, M.-S.; Robertson, B.D.; Gicquel, B.; Stewart, G.R. The Balance of Apoptotic and Necrotic Cell Death in Mycobacterium tuberculosis Infected Macrophages Is Not Dependent on Bacterial Virulence. PLoS ONE 2012, 7, e47573.
  101. Cohen, P.L.; Caricchio, R.; Abraham, V.; Camenisch, T.D.; Jennette, J.C.; Roubey, R.A.; Earp, H.S.; Matsushima, G.; Reap, E.A. Delayed Apoptotic Cell Clearance and Lupus-like Autoimmunity in Mice Lacking the c-mer Membrane Tyrosine Kinase. J. Exp. Med. 2002, 196, 135–140.
  102. Alciato, F.; Sainaghi, P.P.; Sola, D.; Castello, L.M.; Avanzi, G.C. TNF-α, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages. J. Leukoc. Biol. 2010, 87, 869–875.
  103. Shao, W.-H.; Kuan, A.P.; Wang, C.; Abraham, V.; Waldman, M.A.; Vogelgesang, A.; Wittenburg, G.; Choudhury, A.; Tsao, P.Y.; Miwa, T.; et al. Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ B-cell responses. J. Autoimmun. 2010, 35, 368–374.
  104. Wallet, M.A.; Flores, R.R.; Wang, Y.; Yi, Z.; Kroger, C.J.; Mathews, C.E.; Earp, H.S.; Matsushima, G.; Wang, B.; Tisch, R. MerTK regulates thymic selection of autoreactive T cells. Proc. Natl. Acad. Sci. USA 2009, 106, 4810–4815.
  105. Suh, C.-H.; Hilliard, B.; Li, S.; Merrill, J.T.; Cohen, P.L. TAM receptor ligands in lupus: Protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus. Arthritis Res. Ther. 2010, 12, R146.
  106. Zizzo, G.; Hilliard, B.A.; Monestier, M.; Cohen, P.L. Efficient Clearance of Early Apoptotic Cells by Human Macrophages Requires M2c Polarization and MerTK Induction. J. Immunol. 2012, 189, 3508–3520.
  107. Voll, R.E.; Herrmann, M.; Roth, E.A.; Stach, C.; Kalden, J.R.; Girkontaite, I. Immunosuppressive effects of apoptotic cells. Nature 1997, 390, 350–351.
  108. Rothlin, C.V.; Ghosh, S.; Zuniga, E.I.; Oldstone, M.B.; Lemke, G. TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response. Cell 2007, 131, 1124–1136.
  109. Cheong, H.S.; Lee, S.O.; Choi, C.-B.; Sung, Y.-K.; Shin, H.D.; Bae, S.-C. MERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients. Rheumatology 2007, 46, 209–214.
  110. Martinez, F.O.; Sica, A.; Mantovani, A.; Locati, M. Macrophage activation and polarization. Front. Biosci. 2008, 13, 453–461.
  111. Funes, S.C.; Rios, M.; Escobar-Vera, J.; Kalergis, A.M. Implications of macrophage polarization in autoimmunity. Immunology 2018, 154, 186–195.
  112. Matzinger, P.; Guerder, S. Does T-cell tolerance require a dedicated antigen-presenting cell? Nature 1989, 338, 74–76.
  113. Volkmann, A.; Zal, T.; Stockinger, B. Antigen-presenting cells in the thymus that can negatively select MHC class II-restricted T cells recognizing a circulating self antigen. J. Immunol. 1997, 158, 693–706.
  114. Steinman, R.M.; Idoyaga, J. Features of the dendritic cell lineage. Immunol. Rev. 2010, 234, 5–17.
  115. Probst, H.C.; McCoy, K.; Okazaki, T.; Honjo, T.; van den Broek, M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat. Immunol. 2005, 6, 280–286.
  116. Tarbell, K.V.; Petit, L.; Zuo, X.; Toy, P.; Luo, X.; Mqadmi, A.; Yang, H.; Suthanthiran, M.; Mojsov, S.; Steinman, R.M. Dendritic cell–expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med. 2007, 204, 191–201.
  117. Luo, X.; Tarbell, K.V.; Yang, H.; Pothoven, K.; Bailey, S.L.; Ding, R.; Steinman, R.M.; Suthanthiran, M. Dendritic cells with TGF-β1 differentiate naïve CD4+ CD25− T cells into islet-protective Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA 2007, 104, 2821–2826.
  118. Belkaid, Y.; Oldenhove, G. Tuning Microenvironments: Induction of Regulatory T Cells by Dendritic Cells. Immunity 2008, 29, 362–371.
  119. Darrasse-Jèze, G.; Deroubaix, S.; Mouquet, H.; Victora, G.D.; Eisenreich, T.; Yao, K.-H.; Masilamani, R.F.; Dustin, M.L.; Rudensky, A.; Liu, K.; et al. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 2009, 206, 1853–1862.
  120. O’Keeffe, M.; Brodnicki, T.C.; Fancke, B.; Vremec, D.; Morahan, G.; Maraskovsky, E.; Steptoe, R.; Harrison, L.C.; Shortman, K. Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development. Int. Immunol. 2005, 17, 307–314.
  121. Whartenby, K.A.; Calabresi, P.A.; McCadden, E.; Nguyen, B.; Kardian, D.; Wang, T.; Mosse, C.; Pardoll, D.M.; Small, D. Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc. Natl. Acad. Sci. USA 2005, 102, 16741–16746.
  122. Coutant, F.; Pin, J.-J.; Miossec, P. Extensive Phenotype of Human Inflammatory Monocyte-Derived Dendritic Cells. Cells 2021, 10, 1663.
  123. Macri, C.; Pang, E.S.; Patton, T.; O’Keeffe, M. Dendritic cell subsets. In Seminars in Cell & Developmental Biology; Academic Press: Cambridge, MA, USA, 2018; Volume 84, pp. 11–21.
  124. Segura, E.; Touzot, M.; Bohineust, A.; Cappuccio, A.; Chiocchia, G.; Hosmalin, A.; Dalod, M.; Soumelis, V.; Amigorena, S. Human Inflammatory Dendritic Cells Induce Th17 Cell Differentiation. Immunity 2013, 38, 336–348.
  125. Eguíluz-Gracia, I.; Bosco, A.; Dollner, R.; Melum, G.R.; Lexberg, M.H.; Jones, A.C.; Dheyauldeen, S.A.; Holt, P.G.; Bækkevold, E.S.; Jahnsen, F.L. Rapid recruitment of CD14+ monocytes in experimentally induced allergic rhinitis in human subjects. J. Allergy Clin. Immunol. 2016, 137, 1872–1881.e12.
  126. Richter, L.; Landsverk, O.J.B.; Atlasy, N.; Bujko, A.; Yaqub, S.; Horneland, R.; Øyen, O.; Aandahl, E.M.; Lundin, K.E.A.; Stunnenberg, H.G.; et al. Transcriptional profiling reveals monocyte-related macrophages phenotypically resembling DC in human intestine. Mucosal Immunol. 2018, 11, 1512–1523.
  127. Gu, F.-F.; Wu, J.-J.; Liu, Y.-Y.; Hu, Y.; Liang, J.-Y.; Zhang, K.; Li, M.; Wang, Y.; Zhang, Y.-A.; Liu, L. Human Inflammatory Dendritic Cells in Malignant Pleural Effusions Induce Th1 Cell Differentiation. Cancer Immunol. Immunother. 2020, 69, 779–788.
  128. Lugt, B.V.; Riddell, J.; Khan, A.A.; Hackney, J.A.; Lesch, J.; Devoss, J.; Weirauch, M.T.; Singh, H.; Mellman, I. Transcriptional determinants of tolerogenic and immunogenic states during dendritic cell maturation. J. Cell Biol. 2017, 216, 779–792.
  129. Rutella, S.; Danese, S.; Leone, G. Tolerogenic dendritic cells: Cytokine modulation comes of age. Blood 2006, 108, 1435–1440.
  130. Vendelova, E.; Ashour, D.; Blank, P.; Erhard, F.; Saliba, A.-E.; Kalinke, U.; Lutz, M.B. Tolerogenic Transcriptional Signatures of Steady-State and Pathogen-Induced Dendritic Cells. Front. Immunol. 2018, 9, 333.
  131. Obreque, J.; Vega, F.; Torres, A.; Cuitino, L.; Mackern-Oberti, J.P.; Viviani, P.; Kalergis, A.; Llanos, C. Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype. Immunology 2017, 152, 648–659.
  132. Wu, H.J.; Lo, Y.; Luk, D.; Lau, C.S.; Lu, L.; Mok, M.Y. Alternatively activated dendritic cells derived from systemic lupus erythematosus patients have tolerogenic phenotype and function. Clin. Immunol. 2015, 156, 43–57.
  133. Esmaeili, S.; Mahmoudi, M.; Rezaieyazdi, Z.; Sahebari, M.; Tabasi, N.; Sahebkar, A.; Rastin, M. Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics. J. Cell. Biochem. 2018, 119, 7865–7872.
  134. Hossein-Khannazer, N.; Torabi, S.; Hosseinzadeh, R.; Shahrokh, S.; Aghdaei, H.A.; Memarnejadian, A.; Kadri, N.; Vosough, M. Novel cell-based therapies in inflammatory bowel diseases: The established concept, promising results. Hum. Cell 2021, 34, 1289–1300.
  135. Passeri, L.; Marta, F.; Bassi, V.; Gregori, S. Tolerogenic Dendritic Cell-Based Approaches in Autoimmunity. Int. J. Mol. Sci. 2021, 22, 8415.
  136. Adorini, L. Selective Immunointervention in Autoimmune Diseases: Lessons from Multiple Sclerosis. J. Chemother. 2001, 13, 219–234.
  137. Cantorna, M.T. Vitamin D and its role in immunology: Multiple sclerosis, and inflammatory bowel disease. Prog. Biophys. Mol. Biol. 2006, 92, 60–64.
  138. Cutolo, M.; Plebani, M.; Shoenfeld, Y.; Adorini, L.; Tincani, A. Vitamin D Endocrine System and the Immune Response in Rheumatic Diseases. Vitam. Horm. 2011, 86, 327–351.
  139. Lin, J.; Liu, J.; Davies, M.L.; Chen, W. Serum Vitamin D Level and Rheumatoid Arthritis Disease Activity: Review and Meta-Analysis. PLoS ONE 2016, 11, e0146351.
  140. Zou, J.; Thornton, C.; Chambers, E.S.; Rosser, E.C.; Ciurtin, C. Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease. Front. Immunol. 2021, 11, 616483.
  141. Szodoray, P.; Nakken, B.; Gaal, J.; Jonsson, R.; Szegedi, A.; Zold, E.; Szegedi, G.; Brun, J.G.; Gesztelyi, R.; Zeher, M.; et al. The Complex Role of Vitamin D in Autoimmune Diseases. Scand. J. Immunol. 2008, 68, 261–269.
  142. Murdaca, G.; Tonacci, A.; Negrini, S.; Greco, M.; Borro, M.; Puppo, F.; Gangemi, S. Emerging role of vitamin D in autoimmune diseases: An update on evidence and therapeutic implications. Autoimmun. Rev. 2019, 18, 102350.
  143. Cantorna, M.T.; Mahon, B.D. Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence. Exp. Biol. Med. 2004, 229, 1136–1142.
  144. Antico, A.; Tampoia, M.; Tozzoli, R.; Bizzaro, N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun. Rev. 2012, 12, 127–136.
  145. Taha, R.; Abureesh, S.; Alghamdi, S.; Hassan, R.Y.; Cheikh, M.M.; Bagabir, R.A.; Almoallim, H.; Abdulkhaliq, A. The Relationship Between Vitamin D and Infections Including COVID-19: Any Hopes? Int. J. Gen. Med. 2021, 14, 3849–3870.
  146. Souberbielle, J.-C.; Body, J.-J.; Lappe, J.M.; Plebani, M.; Shoenfeld, Y.; Wang, T.; Bischoff-Ferrari, H.; Cavalier, E.; Ebeling, P.R.; Fardellone, P.; et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun. Rev. 2010, 9, 709–715.
  147. Penna, G.; Adorini, L. 1α,25-Dihydroxyvitamin D3Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation. J. Immunol. 2000, 164, 2405–2411.
  148. Cantorna, M.T.; Snyder, L.; Lin, Y.-D.; Yang, L. Vitamin D and 1,25(OH)2D Regulation of T cells. Nutrients 2015, 7, 3011–3021.
  149. Mora, J.R.; Iwata, M.; von Andrian, U.H. Vitamin effects on the immune system: Vitamins A and D take centre stage. Nat. Rev. Immunol. 2008, 8, 685–698.
  150. Daniel, C.; Sartory, N.A.; Zahn, N.; Radeke, H.H.; Stein, J.M. Immune Modulatory Treatment of Trinitrobenzene Sulfonic Acid Colitis with Calcitriol Is Associated with a Change of a T Helper (Th) 1/Th17 to a Th2 and Regulatory T Cell Profile. J. Pharmacol. Exp. Ther. 2008, 324, 23–33.
  151. Adorini, L.; Penna, G. Dendritic cell tolerogenicity: A key mechanism in immunomodulation by vitamin D receptor agonists. Hum. Immunol. 2009, 70, 345–352.
  152. Shoenfeld, Y.; Zandman-Goddard, G.; Stojanovich, L.; Cutolo, M.; Amital, H.; Levy, Y.; Abu-Shakra, M.; Barzilai, O.; Berkun, Y.; Blank, M.; et al. The mosaic of autoimmunity: Hormonal and environmental factors involved in autoimmune diseases—2008. Isr. Med Assoc. J. IMAJ 2008, 10, 8–12.
  153. Zhao, X.; Yuan, Y.; Lin, Y.; Zhang, T.; Bai, Y.; Kang, D.; Li, X.; Kang, W.; Dlodlo, R.A.; Harries, A.D. Vitamin D status of tuberculosis patients with diabetes mellitus in different economic areas and associated factors in China. PLoS ONE 2018, 13, e0206372.
  154. Borba, V.V.; Zandman-Goddard, G.; Shoenfeld, Y. Prolactin and autoimmunity: The hormone as an inflammatory cytokine. Best Pract. Res. Clin. Endocrinol. Metab. 2019, 33, 101324.
  155. Lyadova, I.V.; Panteleev, A.V. Th1 and Th17 Cells in Tuberculosis: Protection, Pathology, and Biomarkers. Mediat. Inflamm. 2015, 2015, 854507.
  156. Maione, F.; Paschalidis, N.; Mascolo, N.; Dufton, N.; Perretti, M.; D’Acquisto, F. Interleukin 17 sustains rather than induces inflammation. Biochem. Pharmacol. 2009, 77, 878–887.
  157. Basile, J.I.; Geffner, L.J.; Romero, M.M.; Balboa, L.; García, C.S.Y.; Ritacco, V.; García, A.; Cuffré, M.; Abbate, E.; López, B.; et al. Outbreaks of Mycobacterium tuberculosis MDR Strains Induce High IL-17 T-Cell Response in Patients with MDR Tuberculosis That Is Closely Associated with High Antigen Load. J. Infect. Dis. 2011, 204, 1054–1064.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Infectious Diseases
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Irina V. Belyaeva
,
Anna N. Kosova
,
Andrei G. Vasiliev
View Times: 408
Revisions: 3 times (View History)
Update Date: 19 Sep 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback