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Topic Review
Circulating Leukocytes in People Mildly Infected by SARS-CoV-2
Mild SARS-CoV-2 infections (n = 22), compared to those that had recovered from other mild respiratory infections (n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1–3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6–9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1–3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6–9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections. 
  • 714
  • 07 Dec 2021
Topic Review
Multistability in Macrophage Activation Pathways
Macrophages are innate immune cells with a dynamic range of reversible activation states including the classical pro-inflammatory (M1) and alternative anti-inflammatory (M2) states. Common regulatory motifs reported for macrophage transitions, such as positive or double-negative feedback loops, exhibit a switchlike behavior, suggesting the bistability of the system.  There are evidence for multistability (including bistability) in macrophage activation pathways at four molecular levels.
  • 713
  • 22 Feb 2022
Topic Review
The Neonatal Immune System
The immune system is a complex network of cells and signals which regulate the host’s response to self and foreign antigens. This delicate system requires substantial regulation to prevent severe damage to the host but is also balanced against the potential damage that could be inflicted if a response is not generated. Thus, responses are primarily dependent on the needs of the hosts and the nature of the signal. In the case of immune stimulation by pathogens, the primary goal of the immune system is to mediate clearance of the pathogen while minimizing damage inflicted to the host by the immune response itself. The adult immune system, which is better studied and understood than is the neonatal one, efficiently generates pro-inflammatory responses which mediate the efficient control of most pathogens. The neonatal immune system, however, is evolved to respond to the unique challenges of the rapid transition from the near-sterile womb to the microbe-rich world beyond. This suddenly introduces millions of new antigens for potential immune recognition and response, a seemingly impossible feat. Therefore, during this transition from near-sterile-fetal to microbe-rich neonatal environment, the immune system is evolved to respond to novel antigens primarily with anti-inflammatory TH2 responses to prevent unnecessary inflammation which can severely harm the infant.
  • 712
  • 29 Jun 2023
Topic Review
Eminent Role of β2-AR in T Cells
Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis.
  • 712
  • 31 Aug 2023
Topic Review
Effects of Dental Calculus-Induced Cytokines on Osteoclastogenesis
Dental calculus (DC) is a common deposit in periodontitis patients. DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokines, such as IL-1β and IL-18, via the NLRP3 inflammasome in macrophages.
  • 711
  • 21 Dec 2021
Topic Review
Synergism of Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade
Radiotherapy and, more recently, PARP inhibitors (PARPis) and immune-checkpoint inhibitors represent effective tools in cancer therapy. Radiotherapy exerts its effects not only by damaging DNA and inducing tumor cell death, but also stimulating anti-tumor immune responses. PARPis are known to exert their therapeutic effects by inhibiting DNA repair, and they may be used in combination with radiotherapy. Both radiotherapy and PARPis modulate inflammatory signals and stimulate type I IFN (IFN-I)-dependent immune activation. However, they can also support the development of an immunosuppressive tumor environment and upregulate PD-L1 expression on tumor cells. When provided as monotherapy, immune-checkpoint inhibitors (mainly antibodies to CTLA-4 and the PD-1/PD-L1 axis) result particularly effective only in immunogenic tumors. Combinations of immunotherapy with therapies that favor priming of the immune response to tumor-associated antigens are, therefore, suitable strategies. The widely explored association of radiotherapy and immunotherapy has confirmed this benefit for several cancers. Association with PARPis has also been investigated in clinical trials. Immunotherapy counteracts the immunosuppressive effects of radiotherapy and/or PARPis and synergies with their immunological effects, promoting and unleashing immune responses toward primary and metastatic lesions (abscopal effect). 
  • 709
  • 22 Feb 2023
Topic Review
Approaches to Enhance Tumor Antigenicity
Cancer immunotherapy has revolutionized the oncology field, but many patients still do not respond to the immunotherapy approaches. One of the main challenges in broadening the range of responses to this type of treatment is the limited source of tumor neoantigens. New approaches must be taken into consideration to overcome these shortcomings. The possibility of making tumors more antigenic represents a promising front to further improve the success of immunotherapy in cancer. 
  • 705
  • 09 Sep 2022
Topic Review
Lymphatic Clearance of Immune Cells in Cardiovascular Disease
The lymphatic vasculature is a vital component of the cardiovascular system, consisting of a blind-ended, highly permeable vascular network, integral in maintaining tissue homeostasis, regulation of interstitial fluid, lipid absorption, fluid drainage, and immune cell trafficking. Its role in immune cell transport is critical in the initiation of the immune response, especially following injury. This is of particular importance in the heart, where the lymphatic vasculature plays a vital role in myocardial healing following cardiac injury. By promoting cell egress or exit from the heart, the lymphatic systems favour cell clearance by way of reduction of the immune cell load in damaged tissue.
  • 704
  • 13 Apr 2022
Topic Review
The Intricate Role of Non-Coding RNAs in DIC
Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, due mainly to the effect of the inflammation on the coagulation system. MicroRNAs, long non-coding RNAs, and circular RNAs are studied in relation to DIC. Specifically, the axis between these non-coding RNAs and the corresponding affected pathway has been identified, including inflammation, alteration of the coagulation cascade, and endothelial damage. 
  • 704
  • 23 Feb 2023
Topic Review
Bovine Immunity and Vitamin D3
Mycobacterium avium subspecies paratuberculosis (MAP) is an environmentally hardy pathogen of ruminants that is transmitted via the fecal-oral route. Transition from subclinical to clinical infection is a dynamic process led by MAP, which survives and replicates in host macrophages. Hallmark clinical symptoms include granulomatous enteritis, watery diarrhea, and significant loss of body condition. Clinical stage disease is accompanied by dysfunctional immune responses and a reduction in circulating vitamin D3. The immunomodulatory role of vitamin D3 in infectious disease has been well established in humans, particularly in Mycobacterium tuberculosis infection. However, significant species differences exist between the immune system of humans and bovines, including effects induced by vitamin D3. 
  • 704
  • 27 Sep 2022
Topic Review
Types of Danger-Associated Molecular Patterns
The innate system is primed to sense “danger signals”, described as damage-associated molecular patterns (DAMPs), and respond to them, usually by activating the immune system and creating a pro-inflammatory environment. These DAMPs are molecules that are inherent to the organism but have a high pro-inflammatory power when they are detected in places where they are not usually present, such as in extracellular or free-form contexts, which is an indicator of tissue damage and produced in surgical processes. DAMPs are molecules inherent to the organism, but which have a high proinflammatory power by activating the inflammasome when detected in places where they are not usually present, such as in extracellular contexts or in free form. The presence of DAMPs is an indicator of tissue damage and can be produced in surgical processes. 
  • 701
  • 07 Mar 2023
Topic Review
Vaccines in Gastrointestinal Malignancies
Gastrointestinal (GI) malignancies are some of the most common malignancies and include colorectal, gastric, esophageal, hepatocellular, and pancreatic carcinomas. Overall five-year survival rates for many of these malignancies are low, with many patients presenting with advanced disease. Thus, it is important to continue to investigate and create novel therapeutic interventions to treat these malignancies.
  • 700
  • 30 Jun 2021
Topic Review
Innate Immunity in Disease and Adaptation to Stress
Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last decades point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation.
  • 700
  • 06 Jun 2022
Topic Review
Gold Nanoparticle-Mediated Gene Editing
Gold nanoparticles (AuNPs) have gained increasing attention as novel drug-delivery nanostructures for the treatment of cancers, infections, inflammations, and other diseases and disorders. They are versatile in design, synthesis, modification, and functionalization. This has many advantages in terms of gene editing and gene silencing, and their application in genetic illnesses. 
  • 699
  • 15 Nov 2022
Topic Review
Inflammasome Structures and Mechanisms of Action
Inflammasome complexes and their integral receptor proteins have essential roles in regulating the innate immune response and inflammation at the post-translational level. Yet despite their protective role, aberrant activation of inflammasome proteins and gain of function mutations in inflammasome component genes seem to contribute to the development and progression of human autoimmune and autoinflammatory diseases. 
  • 698
  • 20 Jul 2023
Topic Review
Toll-Like Receptors in Brief
Toll-like receptors (TLRs) are pivotal components of the innate immune system, acting as vigilant sentinels that detect microbial threats and orchestrate immune responses. This research navigates the intricate world of TLRs, commencing with their discovery, evolutionary significance, and structural attributes. 
  • 696
  • 08 Oct 2023
Topic Review
Myocardial Infarction Guided Emergency Hematopoiesis
“Emergency hematopoiesis” occurs after myocardial infarction (MI) and includes different processes: (1) the amplification of leukocyte production, (2) the maturation of alternative leukocyte subsets and (3) the release of myeloid cells from primary and secondary hematopoietic organs.
  • 694
  • 22 Dec 2022
Topic Review
Helios in the Immune System
The Helios protein (encoded by the IKZF2 gene) is a member of the Ikaros transcription family and it has recently been proposed as a promising biomarker for systemic lupus erythematosus (SLE) disease progression in both mouse models and patients. Helios is beginning to be studied extensively for its influence on the T regulatory (Treg) compartment, both CD4+ Tregs and KIR+/Ly49+ CD8+ Tregs, with alterations to the number and function of these cells correlated to the autoimmune phenomenon.
  • 692
  • 04 Jan 2024
Topic Review
Two-Pore Channels and Ca2+ Homeostasis in Immune Cells
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca2+ from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca2+ signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), were found to trigger the release of Ca2+ from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. 
  • 690
  • 16 May 2022
Topic Review
Molecular Mechanisms of IL18 in Disease
Interleukin 18 (IL18) was originally identified as an inflammation-induced cytokine that is secreted by immune cells. An increasing number of studies have focused on its non-immunological functions, with demonstrated functions for IL18 in energy homeostasis and neural stability. IL18 is reportedly required for lipid metabolism in the liver and brown adipose tissue. Furthermore, IL18 (Il18) deficiency in mice leads to mitochondrial dysfunction in hippocampal cells, resulting in depressive-like symptoms and cognitive impairment. 
  • 689
  • 20 Dec 2023
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