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      The biology of natural killer cells during sepsis

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          Abstract

          <p id="d840257e236">Natural killer (NK) cells are large granular lymphocytes largely recognized for their importance in tumour surveillance and the host response to viral infections. However, as the major innate lymphocyte population, NK cells also coordinate early responses to bacterial infections by amplifying the antimicrobial functions of myeloid cells, especially macrophages, by production of interferon‐ <i>γ</i> (IFN‐ <i>γ</i>). Alternatively, excessive NK cell activation and IFN‐ <i>γ</i> production can amplify the systemic inflammatory response during sepsis resulting in increased physiological dysfunction and organ injury. Our understanding of NK cell biology during bacterial infections and sepsis is mostly derived from studies performed in mice. Human studies have demonstrated a correlation between altered NK cell functions and outcomes during sepsis. However, mechanistic understanding of NK cell function during human sepsis is limited. In this review, we will review the current understanding of NK cell biology during sepsis and discuss the challenges associated with modulating NK cell function during sepsis for therapeutic benefit. </p>

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          Most cited references83

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          Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.

          Stress-inducible MICA, a distant homolog of major histocompatibility complex (MHC) class I, functions as an antigen for gammadelta T cells and is frequently expressed in epithelial tumors. A receptor for MICA was detected on most gammadelta T cells, CD8+ alphabeta T cells, and natural killer (NK) cells and was identified as NKG2D. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gammadelta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses.
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            Septic shock.

            Septic shock, the most severe complication of sepsis, is a deadly disease. In recent years, exciting advances have been made in the understanding of its pathophysiology and treatment. Pathogens, via their microbial-associated molecular patterns, trigger sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. Proinflammatory mediators that contribute to eradication of invading microorganisms are produced, and anti-inflammatory mediators control this response. The inflammatory response leads to damage to host tissue, and the anti-inflammatory response causes leucocyte reprogramming and changes in immune status. The time-window for interventions is short, and treatment must promptly control the source of infection and restore haemodynamic homoeostasis. Further research is needed to establish which fluids and vasopressors are best. Some patients with septic shock might benefit from drugs such as corticosteroids or activated protein C. Other therapeutic strategies are under investigation, including those that target late proinflammatory mediators, endothelium, or the neuroendocrine system.
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              CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity.

              Natural killer (NK) cells are innate lymphocytes that provide cytokines critical for early host defense against pathogens. One subset of human NK cells (CD56(bright)) constitutively expresses the high-affinity interleukin 2 (IL-2) receptor and produces immunoregulatory cytokines. Here, we demonstrate that CD56(bright) NK cells are present in human lymph nodes and that endogenous T cell-derived IL-2, acting through the NK high-affinity IL-2 receptor, costimulates CD56(bright) NK cells to secrete IFN-gamma. Thus, adaptive immunoregulators influence innate cytokine production, which in turn may influence the developing antigen-specific immune response. These data show a dynamic interaction between innate and adaptive human lymphocytes and emphasize the importance of studying interactions between immune components to understand the immune response as a whole.
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                Author and article information

                Journal
                Immunology
                Immunology
                Wiley
                00192805
                February 2018
                February 2018
                November 16 2017
                : 153
                : 2
                : 190-202
                Affiliations
                [1 ]Department of Anesthesiology; Vanderbilt University Medical Center; Nashville TN USA
                [2 ]Department of Pathology, Microbiology and Immunology; Vanderbilt University Medical Center; Nashville TN USA
                Article
                10.1111/imm.12854
                5765373
                29064085
                62a6f044-afc4-4ee8-9279-811c724a310b
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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