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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. 
  • 795
  • 16 May 2022
Topic Review
Effects of Circadian Disruption on Innate Immunity
Circadian rhythms control almost all aspects of physiology and behavior, allowing temporal synchrony of these processes between each other, as well as with the external environment. In the immune system, daily rhythms of leukocyte functions can determine the strength of the immune response, thereby regulating the efficiency of defense mechanisms to cope with infections or tissue injury. The natural light/dark cycle is the prominent synchronizing agent perceived by the circadian clock, but this role of light is highly compromised by irregular working schedules and unintentional exposure to artificial light at night (ALAN).
  • 795
  • 28 Nov 2022
Topic Review
Neutrophils and Flaviviruses
Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. 
  • 792
  • 24 Nov 2021
Topic Review
Understanding of Immunity, Pathogenesis and Management of COVID-19
Coronaviruses represent a diverse family of enveloped positive-sense single stranded RNA viruses. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2, is a highly contagious respiratory disease transmissible mainly via close contact and respiratory droplets which can result in severe, life-threatening respiratory pathologies. It is understood that glutathione, a naturally occurring antioxidant known for its role in immune response and cellular detoxification, is the target of various proinflammatory cytokines and transcription factors resulting in the infection, replication, and production of reactive oxygen species. This leads to more severe symptoms of COVID-19 and increased susceptibility to other illnesses such as tuberculosis.
  • 792
  • 08 Sep 2022
Topic Review
Targeting Immunosuppressive Adenosine Signaling
The tumor microenvironment regulates many aspects of cancer progression and anti-tumor immunity. Cancer cells employ a variety of immunosuppressive mechanisms to dampen immune cell function in the tumor microenvironment. While immunotherapies that target these mechanisms, such as immune checkpoint blockade, have had notable clinical success, resistance is common, and there is an urgent need to identify additional targets. Extracellular adenosine, a metabolite of ATP, is found at high levels in the tumor microenvironment and has potent immunosuppressive properties. Targeting members of the adenosine signaling pathway represents a promising immunotherapeutic modality that can potentially synergize with conventional anti-cancer treatment strategies. 
  • 786
  • 25 May 2023
Topic Review
Role of Antimicrobial Peptides in Autoimmune Disorders
The antimicrobial peptides are present in many parts of the human body such as skin, mucosae, etc., that are exposed to microbes. AMPs are typically produced together as a mixture of several peptides, with tissue-specific unique AMP combinations. While specific AMPs are more prevalent in particular parts of the body, very few are exclusively produced by a single tissue or cell type. Almost all AMPs have multiple functions. AMPs, such as defensins and cathelicidins, were initially identified and studied due to their antimicrobial properties. Defensins and cathelicidins possess various immunomodulatory activities apart from their broad spectrum of activity against pathogens.
  • 786
  • 09 Jun 2023
Topic Review
Immune Cells in Oxi-Inflamm-Aging
Since immune cells need to produce oxidant and inflammatory compounds to carry out their defensive function, when uncontrolled, they may be responsible for the generation of oxidative-inflammatory stress that would not only cause their functional deterioration (immunosenescence) but could also increase these stresses in the body, accelerating the aging process. Given that phagocytes (neutrophils in humans and macrophages in mice) are the main immune cell type that generates oxidants throughout the “respiratory burst” in which NADPH oxidase and xanthine oxidase enzymes participate, they were proposed to play a central role in oxi-inflamm-aging.
  • 783
  • 24 Nov 2021
Topic Review
Clinical Relevance of Circulating Tumor Cells in Immunology
Circulating tumor cells (CTCs) are a heterogeneous population of tumor cells that have shed from a tumor into the lymphatics and vasculature, ultimately disseminating into blood circulation. Immune modulation is a hallmark of cancer. Cancer–immune interaction shapes the course of disease progression at every step of tumorigenesis, including metastasis, of which circulating tumor cells (CTCs) are regarded as an indicator. 
  • 781
  • 07 Mar 2022
Topic Review
Leishmania for Developing a Novel Vaccine Platform
“Bugs as drugs” in medicine encompasses the use of microbes to enhance the efficacy of vaccination, such as the delivery of vaccines by Leishmania—the protozoan etiological agent of leishmaniasis. This novel approach is appraised in light of the successful development of vaccines for Covid-19. All relevant aspects of this pandemic are summarized to provide the necessary framework in contrast to leishmaniasis.
  • 781
  • 23 Feb 2022
Topic Review
Dendritic Cells as Multifaceted Orchestrators of Immune Responses
Immune-mediated inflammatory diseases (IMIDs) are a group of autoimmune and chronic inflammatory disorders with constantly increasing prevalence in the modern world. The vast majority of IMIDs develop as a consequence of complex mechanisms dependent on genetic, epigenetic, molecular, cellular, and environmental elements, that lead to defects in immune regulatory guardians of tolerance, such as dendritic (DCs) cells.
  • 781
  • 24 Nov 2022
Topic Review
Molecular Basis of Ferroptosis
Ferroptosis is a recently recognized iron-dependent form of non-apoptotic regulated cell death (RCD) characterized by lipid peroxide accumulation to lethal levels. Cancer cells, which show an increased iron dependency to enable rapid growth, seem vulnerable to ferroptosis. There is also increasing evidence that ferroptosis might be immunogenic and therefore could synergize with immunotherapies. Hepatocellular carcinoma (HCC) is the most common primary liver tumor with a low survival rate due to frequent recurrence and limited efficacy of conventional chemotherapies, illustrating the urgent need for novel drug approaches or combinatorial strategies. Immunotherapy is a new treatment approach for advanced HCC patients.
  • 776
  • 03 Mar 2022
Topic Review
Endosomal TLR Agonists Improving NK Cell Function
Toll-like receptors (TLRs) are the most well-defined pattern recognition receptors (PRR) of several cell types recognizing pathogens and triggering innate immunity. TLRs are also expressed on tumor cells and tumor microenvironment (TME) cells, including natural killer (NK) cells. Cell surface TLRs primarily recognize extracellular ligands from bacteria and fungi, while endosomal TLRs recognize microbial DNA or RNA. TLR engagement activates intracellular pathways leading to the activation of transcription factors regulating gene expression of several inflammatory molecules. Endosomal TLR agonists may be considered as new immunotherapeutic adjuvants for dendritic cell (DC) vaccines able to improve anti-tumor immunity and cancer patient outcomes.
  • 776
  • 09 Mar 2023
Topic Review
Inflammasome-Mediated Cytokines
Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor.
  • 769
  • 07 Feb 2023
Topic Review
Immunotherapy during the Immediate Perioperative Period
Tumor excision is a necessary life-saving procedure in most solid cancers. However, surgery and the days before and following it, known as the immediate perioperative period (IPP), entail numerous prometastatic processes, including the suppression of antimetastatic immunity and direct stimulation of minimal residual disease (MRD). Thus, the IPP is pivotal in determining long-term cancer outcomes, presenting a short window of opportunity to circumvent perioperative risk factors by employing several therapeutic approaches, including immunotherapy. Nevertheless, immunotherapy is rarely examined or implemented during this short timeframe, due to both established and hypothetical contraindications to surgery. This entry summarizes existing and potential immuno-theraputic approaches to exploit the immediate perioperative period to prevent future metastatic disease.
  • 769
  • 23 Aug 2023
Topic Review
B-Cell Activating Factor in IBD
B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily. BAFF is predominantly produced by myeloid cells (monocytes, macrophages, dendritic cells and neutrophils), and its main role is regulation of mature B cell survival and differentiation into antibody-producing plasma cells. Overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus (SLE), where BAFF-inhibitor belimumab was approved for treatment.
  • 767
  • 27 Jan 2022
Topic Review
Monoclonal Antibodies
The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected.
  • 765
  • 19 Feb 2024
Topic Review
HIV Vaccine Development
An HIV vaccine can be either a preventive vaccine or a therapeutic vaccine, which means it can either protect individuals from being infected with HIV or treat HIV-infected individuals. And it can either induce an immune response against HIV (active vaccination approach) or consist of preformed antibodies against HIV (passive vaccination approach). There is currently no licensed HIV vaccine on the market, but multiple research projects are trying to find an effective vaccine. Evidence observed from humans shows that a vaccine may be possible: Some, but certainly not all, HIV-infected individuals naturally produce broadly neutralizing antibodies which keep the virus suppressed, and these people remain asymptomatic for decades. Potential broadly neutralizing antibodies have been cloned in the laboratory (monoclonal antibodies) and are being tested in passive vaccination clinical trials. Many trials have shown no efficacy, but one HIV vaccine regimen, RV 144, has been shown to prevent HIV in some individuals in Thailand. The urgency of the search for a vaccine against HIV stems from the AIDS-related death toll of over 35 million people since 1981. In 2002, AIDS became the primary cause of death due to an infectious agent in Africa. Alternative medical treatments to a vaccine exist. For the treatment of HIV-infected individuals, highly active antiretroviral therapy (HAART) medication has been demonstrated to provide many benefits to HIV-infected individuals, including improved health, increased lifespan, control of viremia, and prevention of transmission to babies and partners. HAART must be taken lifelong without interruption to be effective, and cannot cure HIV. Options for the prevention of HIV infection in HIV-uninfected individuals include safer sex (for example condom use), antiretroviral strategies (pre-exposure prophylaxis and post-exposure prophylaxis) and medical male circumcision. Vaccination has proved a powerful public health tool in vanquishing other diseases, and an HIV vaccine is generally considered as the most likely, and perhaps the only way by which the HIV pandemic can be halted. However, HIV remains a challenging target for a vaccine.
  • 764
  • 27 Oct 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. 
  • 764
  • 20 Jul 2023
Topic Review
Neurocognitive Symptoms Due to Respiratory infections
Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations.
  • 763
  • 18 Jan 2022
Topic Review
IL-17-Member Family
T-helper 17 (Th17) cells represent a subpopulation of CD4+ T lymphocytes that play an essential role in defense against pathogens. Th17 cells are distinguished from Th1 and Th2 cells by their ability to produce members of the interleukin-17 (IL-17) family, namely IL-17A and IL-17F. IL-17 in turn induces several target cells to synthesize and release cytokines, chemokines, and metalloproteinases, thereby amplifying the inflammatory cascade. Th17 cells reside predominantly in the lamina propria of the mucosa.
  • 762
  • 03 Jan 2023
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