Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Immunology. 2018 Feb;153(2):190-202. doi: 10.1111/imm.12854. Epub 2017 Nov 16.
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-γ (IFN-γ). Alternatively, excessive NK cell activation and IFN-γ 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.
自然杀伤 (NK) 细胞是一种大型颗粒淋巴细胞，其在肿瘤监测和宿主对病毒感染的反应中的重要性已得到广泛认可。然而，作为主要的先天淋巴细胞群体，NK 细胞还通过产生干扰素-γ (IFN-γ) 来放大髓样细胞（尤其是巨噬细胞）的抗菌功能，从而协调对细菌感染的早期反应。相反，过度的 NK 细胞激活和 IFN-γ 产生会在败血症期间放大全身炎症反应，导致生理功能障碍和器官损伤增加。我们对细菌感染和败血症期间 NK 细胞生物学的理解主要来自于在小鼠中进行的研究。人类研究表明，在败血症期间，NK 细胞功能改变与结局之间存在相关性。然而，对人类败血症期间 NK 细胞功能的机制理解有限。在这篇综述中，我们将回顾败血症期间 NK 细胞生物学的现有理解，并讨论在败血症期间调节 NK 细胞功能以获得治疗益处所面临的挑战。
