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.

中文翻译：

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天然杀伤细胞的分化和适应性抗疟疾免疫。

天然杀伤细胞利用多种效应器机制来靶向细胞内病原体。天然杀伤（NK）细胞激活途径的分化沿连续过程发生，从对先天性促炎性细胞因子和应激诱导的宿主配体的依赖一直到与后天获得的免疫反应产生的信号相互作用。重要的是，NK细胞谱系的功能分化程度会影响与感染了病毒，细菌，真菌和寄生虫的宿主细胞相互作用的程度和特异性。单个人拥有种类繁多的不同NK细胞克隆，每个克隆都具有沿着该功能分化途径变化的能力，将它们结合在一起时，会对不同的感染产生独特的个体反应。在这里，我们总结了这些NK细胞分化事件，审查了感染疟疾的宿主细胞与NK细胞直接相互作用的证据，并评估了由疟原虫相关分子模式诱导的先天性炎症信号如何影响NK细胞的间接激活和功能。最后，我们讨论了证据，即抗疟疾免疫与发展的NK分化同时发展，同时丧失对炎症信号的依赖，并且NK细胞具有更精确的靶向疟原虫的精确能力，特别是通过抗体依赖性机制。