1. Differentiation and adaptation of natural killer cells for anti-malarial immunity.
- Author
-
Goodier MR, Wolf AS, and Riley EM
- Subjects
- Adaptive Immunity, Animals, Biomarkers, Cell Differentiation genetics, Cytokines metabolism, Disease Models, Animal, Gene-Environment Interaction, Host-Parasite Interactions genetics, Humans, Immunity, Innate, Inflammation Mediators metabolism, Killer Cells, Natural cytology, Killer Cells, Natural metabolism, Lymphocyte Activation genetics, Lymphocyte Activation immunology, Malaria genetics, Malaria metabolism, Plasmodium falciparum immunology, Adaptation, Physiological immunology, Cell Differentiation immunology, Host-Parasite Interactions immunology, Killer Cells, Natural immunology, Malaria immunology, Malaria parasitology, Plasmodium immunology
- Abstract
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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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