Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK.
Department of Infection and Immunity, University College London, London, UK.
Immunol Rev. 2020 Jan;293(1):25-37. doi: 10.1111/imr.12798. Epub 2019 Nov 24.
Natural killer cells employ a diverse arsenal of effector mechanisms to target intracellular pathogens. Differentiation of natural killer (NK) cell activation pathways occurs along a continuum from reliance on innate pro-inflammatory cytokines and stress-induced host ligands through to interaction with signals derived from acquired immune responses. Importantly, the degree of functional differentiation of the NK cell lineage influences the magnitude and specificity of interactions with host cells infected with viruses, bacteria, fungi, and parasites. Individual humans possess a vast diversity of distinct NK cell clones, each with the capacity to vary along this functional differentiation pathway, which - when combined - results in unique individual responses to different infections. Here we summarize these NK cell differentiation events, review evidence for direct interaction of malaria-infected host cells with NK cells and assess how innate inflammatory signals induced by malaria parasite-associated molecular patterns influence the indirect activation and function of NK cells. Finally, we discuss evidence that anti-malarial immunity develops in parallel with advancing NK differentiation, coincident with a loss of reliance on inflammatory signals, and a refined capacity of NK cells to target malaria parasites more precisely, particularly through antibody-dependent mechanisms.
自然杀伤 (NK) 细胞利用多种效应机制靶向细胞内病原体。NK 细胞激活途径的分化沿着从依赖先天促炎细胞因子和应激诱导的宿主配体到与获得性免疫反应衍生的信号相互作用的连续体发生。重要的是，NK 细胞谱系的功能分化程度影响与感染病毒、细菌、真菌和寄生虫的宿主细胞相互作用的幅度和特异性。个体人类拥有大量不同的 NK 细胞克隆，每个克隆都具有沿着这条功能分化途径变化的能力，这些能力结合在一起导致对不同感染的独特个体反应。在这里，我们总结了这些 NK 细胞分化事件，回顾了疟疾感染宿主细胞与 NK 细胞直接相互作用的证据，并评估了疟疾寄生虫相关分子模式诱导的先天炎症信号如何影响 NK 细胞的间接激活和功能。最后，我们讨论了抗疟免疫与 NK 分化同时发展的证据，这与对炎症信号的依赖降低以及 NK 细胞更精确地靶向疟疾寄生虫的能力相一致，特别是通过抗体依赖性机制。
