Contributions of natural killer cells to the immune response against Plasmodium

Natural killer (NK) cells are important innate effector cells that are well described in their ability to kill virally-infected cells and tumors. However, there is increasing appreciation for the role of NK cells in the control of other pathogens, including intracellular parasites such as Plasmodium, the cause of malaria. NK cells may be beneficial during the early phase of Plasmodium infection—prior to the activation and expansion of antigen-specific T cells—through cooperation with myeloid cells to produce inflammatory cytokines like IFNγ. Recent work has defined how Plasmodium can activate NK cells to respond with natural cytotoxicity, and inhibit the growth of parasites via antibody-dependent cellular cytotoxicity mechanisms (ADCC). A specialized subset of adaptive NK cells that are negative for the Fc receptor γ chain have enhanced ADCC function and correlate with protection from malaria. Additionally, production of the regulatory cytokine IL-10 by NK cells prevents overt pathology and death during experimental cerebral malaria. Now that conditional NK cell mouse models have been developed, previous studies need to be reevaluated in the context of what is now known about other immune populations with similarity to NK cells (i.e., NKT cells and type I innate lymphoid cells). This brief review summarizes recent findings which support the potentially beneficial roles of NK cells during Plasmodium infection in mice and humans. Also highlighted are how the actions of NK cells can be explored using new experimental strategies, and the potential to harness NK cell function in vaccination regimens.