Signature of NK cells that are enriched for IL-10 production in malaria infection history subjects

Plasmodium falciparum infection can trigger high levels of inflammation that lead to fever and sometimes severe disease. People living in malaria-endemic areas gradually develop resistance and control both parasite numbers and the inflammatory response. Adaptive Natural Killer (NK) cells correlate with reduced parasite load and protection from symptoms. However, additional NK cell immunoregulatory roles may lower inflammation and reduce fever induction. We previously found that murine NK cell production of IL-10 can protect mice from experimental cerebral malaria. Human NK cells can also secrete IL-10, but it was unknown what NK cell subsets produce IL-10 and if this is affected by malaria infection history. Here, we show that NK cells from subjects with malaria history make significantly more IL-10 than subjects with no malaria history. We then determined the proportions of NK cells that are cytotoxic and produce interferon g (IFNg) and/or IL-10 and identified a signature of adaptive and checkpoint molecules on IL-10 producing NK cells. Lastly, we find that co-culture with primary monocytes, Plasmodium-infected RBCs, and antibody induces IL-10 production by NK cells. These data suggest that NK cells may help with protection from malaria because of IL-10 induction.