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Related Concept Videos

Immune Surveillance by NK Cells and Phagocytes01:25

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Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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Analysis of Human Natural Killer Cell Metabolism
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IL-15 Enables Septic Shock by Maintaining NK Cell Integrity and Function.

Yin Guo1, Liming Luan2, Naeem K Patil2

  • 1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37212; and.

Journal of Immunology (Baltimore, Md. : 1950)
|December 30, 2016
PubMed
Summary

Interleukin-15 (IL-15) maintains natural killer (NK) and memory CD8+ T cells, exacerbating septic shock. Blocking IL-15 protects against sepsis by depleting these cells, highlighting IL-15

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Area of Science:

  • Immunology
  • Sepsis Pathogenesis
  • Cellular Immunity

Background:

  • Interleukin-15 (IL-15) is crucial for natural killer (NK) and memory CD8+ T cell development and function.
  • NK and CD8+ T cells are implicated in the pathology of septic shock.
  • Regulatory factors for NK and CD8+ T cell activity during sepsis remain incompletely understood.

Purpose of the Study:

  • To investigate the role of IL-15 in sepsis pathogenesis.
  • To test the hypothesis that IL-15 promotes sepsis by preserving NK and memory CD8+ T cell integrity.

Main Methods:

  • Assessment of sepsis in IL-15-deficient (knockout, KO) mice.
  • Administration of IL-15 superagonist (IL-15 SA) and IL-15-neutralizing antibody (M96) in septic models.
  • Evaluation of survival, hypothermia, cytokine production, and immune cell populations (NK, CD8+ T cells, IFN-γ).

Main Results:

  • IL-15 KO mice exhibited improved survival, reduced hypothermia, and lower proinflammatory cytokine levels during septic shock.
  • IL-15 SA treatment restored mortality in IL-15 KO mice by regenerating NK and memory CD8+ T cells.
  • Early administration of IL-15-neutralizing antibody (M96) conferred protection against sepsis by depleting NK cells.
  • IL-15 SA exacerbated endotoxin shock and cecal ligation and puncture-induced sepsis, effects mitigated by NK cell or IFN-γ depletion.

Conclusions:

  • Endogenous IL-15 facilitates septic shock development by maintaining NK cell numbers and integrity.
  • Exogenous IL-15 exacerbates sepsis severity through NK cell activation and enhanced IFN-γ production.
  • Targeting IL-15 or its downstream effectors (NK cells, IFN-γ) represents a potential therapeutic strategy for sepsis.