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Cell Mar 2020The study of innate immunity and its link to inflammation and host defense encompasses diverse areas of biology, ranging from genetics and biophysics to signal... (Review)
Review
The study of innate immunity and its link to inflammation and host defense encompasses diverse areas of biology, ranging from genetics and biophysics to signal transduction and physiology. Central to our understanding of these events are the Toll-like receptors (TLRs), an evolutionarily ancient family of pattern recognition receptors. Herein, we describe the mechanisms and consequences of TLR-mediated signal transduction with a focus on themes identified in the TLR pathways that also explain the operation of other immune signaling pathways. These themes include the detection of conserved microbial structures to identify infectious agents and the use of supramolecular organizing centers (SMOCs) as signaling organelles that ensure digital cellular responses. Further themes include mechanisms of inducible gene expression, the coordination of gene regulation and metabolism, and the influence of these activities on adaptive immunity. Studies in these areas have informed the development of next-generation therapeutics, thus ensuring a bright future for research in this area.
Topics: Adaptive Immunity; Animals; Humans; Immunity, Innate; Inflammation; Organelles; Signal Transduction; Toll-Like Receptors
PubMed: 32164908
DOI: 10.1016/j.cell.2020.02.041 -
The New England Journal of Medicine Feb 2023
Review
Topics: Humans; Acute-Phase Proteins; Immunity, Humoral; Immunity, Innate
PubMed: 36724330
DOI: 10.1056/NEJMra2206346 -
Frontiers in Immunology 2022Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for... (Review)
Review
Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host's defense against infectious diseases, autoimmune diseases, and cancer.
Topics: Adaptive Immunity; Immunity, Cellular; Immunity, Innate; Signal Transduction; Toll-Like Receptors
PubMed: 35309296
DOI: 10.3389/fimmu.2022.812774 -
The Yale Journal of Biology and Medicine Mar 2020Psoriasis is a frequent inflammatory skin disease. Fundamental research on the pathogenesis of psoriasis has substantially increased our understanding of skin... (Review)
Review
Psoriasis is a frequent inflammatory skin disease. Fundamental research on the pathogenesis of psoriasis has substantially increased our understanding of skin immunology, which has helped to introduce innovative and highly effective therapies. Psoriasis is a largely T lymphocyte-mediated disease in which activation of innate immune cells and pathogenic T cells result in skin inflammation and hyperproliferation of keratinocytes. B cells have thus far largely been neglected regarding their role for the pathogenesis of psoriasis. However, recent data shed light on their role in inflammatory skin diseases. Interestingly, interleukin (IL)-10-producing regulatory B cells have been assumed to ameliorate psoriasis. In this review, we will discuss the development of disease, pathogenicity, and current developments in therapeutic options. We describe different roles of T cells, B cells, and cytokines for the immunopathology and disease course of psoriasis.
Topics: Biological Products; Humans; Immunity, Innate; Immunosuppressive Agents; Psoriasis; Skin
PubMed: 32226340
DOI: No ID Found -
Nature Reviews. Nephrology Jan 2023Trained immunity is a functional state of the innate immune response and is characterized by long-term epigenetic reprogramming of innate immune cells. This concept... (Review)
Review
Trained immunity is a functional state of the innate immune response and is characterized by long-term epigenetic reprogramming of innate immune cells. This concept originated in the field of infectious diseases - training of innate immune cells, such as monocytes, macrophages and/or natural killer cells, by infection or vaccination enhances immune responses against microbial pathogens after restimulation. Although initially reported in circulating monocytes and tissue macrophages (termed peripheral trained immunity), subsequent findings indicate that immune progenitor cells in the bone marrow can also be trained (that is, central trained immunity), which explains the long-term innate immunity-mediated protective effects of vaccination against heterologous infections. Although trained immunity is beneficial against infections, its inappropriate induction by endogenous stimuli can also lead to aberrant inflammation. For example, in systemic lupus erythematosus and systemic sclerosis, trained immunity might contribute to inflammatory activity, which promotes disease progression. In organ transplantation, trained immunity has been associated with acute rejection and suppression of trained immunity prolonged allograft survival. This novel concept provides a better understanding of the involvement of the innate immune response in different pathological conditions, and provides a new framework for the development of therapies and treatment strategies that target epigenetic and metabolic pathways of the innate immune system.
Topics: Humans; Trained Immunity; Immunity, Innate; Macrophages; Monocytes; Inflammation
PubMed: 36253509
DOI: 10.1038/s41581-022-00633-5 -
Current Opinion in Cell Biology Aug 2019The mammalian innate immune system serves as the front line of the host to eliminate invading pathogens. The receptors that sense invading pathogens or the... (Review)
Review
The mammalian innate immune system serves as the front line of the host to eliminate invading pathogens. The receptors that sense invading pathogens or the pathogen-associated molecules localized at various membrane compartments that include the plasma membrane, endosomes, and the endoplasmic reticulum. Intriguingly, growing evidence indicates that the sites of pathogen detection do not always represent the site where innate immune signal is triggered. Rather, pathogen detection often induces translocation of the receptors by membrane trafficking. Furthermore, dysregulated membrane trafficking of the receptors renders the host susceptible to infection or prone to autoinflammatory diseases. These findings underscore the critical role of membrane trafficking in the innate immunity. In this review, we highlight emerging issues regarding PRRs and membrane trafficking, with the particular focus on STING and TLR4, the activity of which is tightly regulated by membrane trafficking.
Topics: Humans; Immunity, Innate; Signal Transduction
PubMed: 30875551
DOI: 10.1016/j.ceb.2019.02.002 -
Military Medical Research 2017The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut... (Review)
Review
The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development. The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses, influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.
Topics: Gastrointestinal Microbiome; Humans; Immunity, Innate; Immunity, Mucosal; Intestines; Microbial Interactions
PubMed: 28465831
DOI: 10.1186/s40779-017-0122-9 -
Cells Mar 2020The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in... (Review)
Review
The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in all ER components and machineries. The ER stress sensor pathways, including IRE1/sXBP1, PERK/EIf2 and ATF6, orchestrate the major regulatory circuits to ensure ER homeostasis. The embryonic or postnatal lethality that occurs upon genetic depletion of these sensors reveals the essential role of the ER stress pathway in cell biology. In contrast, the impairment or excessive activation of ER stress has been reported to cause or aggravate several diseases such as atherosclerosis, diabetes, NAFDL/NASH, obesity and cancer. Being part of innate immunity, myeloid cells are the first immune cells entering the inflammation site. Upon entry into a metabolically stressed disease environment, activation of ER stress occurs within the myeloid compartment, leading to the modulation of their phenotype and functions. In this review, we discuss causes and consequences of ER stress activation in the myeloid compartment with a special focus on the crosstalk between ER, innate signaling and metabolic environments.
Topics: Endoplasmic Reticulum Stress; Humans; Immunity, Innate
PubMed: 32178254
DOI: 10.3390/cells9030695 -
Nature Reviews. Immunology Dec 2008Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of... (Review)
Review
Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
Topics: Animals; Cytokines; Humans; Immunity, Innate; Inflammation; Macrophage Activation; Macrophages; Wound Healing
PubMed: 19029990
DOI: 10.1038/nri2448 -
Cold Spring Harbor Perspectives in... Jan 2015Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system.... (Review)
Review
Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. They also recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses.
Topics: Chemokines; Homeostasis; Humans; Immunity, Innate; Inflammation
PubMed: 25635046
DOI: 10.1101/cshperspect.a016303