Natural killer cells in sepsis: Underprivileged innate immune cells

Abstract

Sepsis is a devastating health condition originating due to the dysregulated immune response in response to the severe systemic infection. The innate immune system serves as the first line of defense against invading pathogens, and the failure to clear the infection leads to the development of sepsis via generation of a proinflammatory immune response. Natural Killer (NK) cells are highly recognized potent innate immune cells that play a very important role in the generation of an antiviral and antitumor immune response. These are also unique innate immune cells due to the existence of NK cell-mediated memory due to the process of education and learning as shown by the cells of adaptive immunity. However, developing data has shown the importance of NK cells in mounting a potent immune response against invading bacterial pathogens that if not contained accordingly may lead to the development of sepsis. Thus, the present review article is designed to highlight the previously unrecognized function of NK cells during sepsis as indicated by both clinical and experimental animal-based findings. However, a brief introduction regarding their development, subtypes, and function is also mentioned before describing their role in sepsis. Thereafter, the subsequent section is included describing the NK cell immunometabolic reprogramming during homeostasis, infection, and sepsis. NK cell immune memory and their therapeutic targeting to manage the sepsis as a future therapeutic approach emphasized before closing the manuscript.

Keywords: IFN-γ; Immunometabolism; NK cells; Sepsis; Septic shock; Severe sepsis.