NK Cells: Uncertain Allies against Malaria

Abstract

Until recently, studies of natural killer (NK) cells in infection have focused almost entirely on their role in viral infections. However, there is an increasing awareness of the potential for NK cells to contribute to the control of a wider range of pathogens, including intracellular parasites such as Plasmodium spp. Given the high prevalence of parasitic diseases in the developing world and the devastating effects these pathogens have on large numbers of vulnerable people, investigating interactions between NK cells and parasitized host cells presents the opportunity to reveal novel immunological mechanisms with the potential to aid efforts to eradicate these diseases. The capacity of NK cells to produce inflammatory cytokines early after malaria infection, as well as a possible role in direct cytotoxic killing of malaria-infected cells, suggests a beneficial impact of NK cells in this disease. However, NK cells may also contribute to overproduction of pro-inflammatory cytokines and the consequent immunopathology. As comparatively little is known about the role of NK cells later in the course of infection, and growing evidence suggests that heterogeneity in NK cell responses to malaria may be influenced by KIR/HLA interactions, a better understanding of the mechanisms by which NK cells might directly interact with parasitized cells may reveal a new role for these cells in the course of malaria infection.

Natural killer cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity

“…Earlier studies have described direct lysis of iRBCs by NK cells in the 60 absence of Abs or Ab-dependent inhibition of P. falciparum growth by NK cells (Mavoungou,61 Luty, & Kremsner, 2003; Orago & Facer, 1991). However, other studies have not confirmed such 62 results (Wolf et al, 2017). Here, we present a detailed study of the activity of primary, 63 unstimulated human NK cells mixed with RBCs, infected or not by P.f., and evaluate the NK cell 64 responses using several different quantitative assays.…”

“…Previous work has shown that IL-2 produced by T cells following malaria infection or injection 306 of a malaria vaccine activates IFN-g production by NK cells (Wolf et al, 2017). In addition, P.f.…”

Immune effector mechanisms in malaria: An update focusing on human immunity

“…Natural killer (NK) cells are activated by cytokines (IL12, IL15 and IL18) secreted by monocytes/macrophages and DCs during infection, and experiments demonstrating their direct cytotoxic killing of parasitized‐RBCs have been reviewed in detail elsewhere . NK cell production of pro‐inflammatory cytokines, such as IFNγ also contribute to the immunopathology associated with malaria .…”

Vaccinating for natural killer cell effector functions

“…The role of NK cells in natural immunity or vaccine‐induced protection against malaria infection remains to be established . NK cell activation has been described to varying degrees in different experimental murine models and NK cells have been shown to contribute directly to the elimination of Plasmodium falciparum ‐infected red blood cells (RBC) in a humanised mouse model .…”

“…The role of NK cells in natural immunity or vaccine-induced protection against malaria infection remains to be established. 89 NK cell activation has been described to varying degrees in different experimental murine models 90,91 and NK cells have been shown to contribute directly to the elimination of Plasmodium falciparuminfected red blood cells (RBC) in a humanised mouse model. 92 In vitro studies of human PBMC show NK cells are readily activated by P. falciparum-infected RBC; the resulting NK cell proliferation, IFN-c production, CD25 and CD69 expression were further demonstrated to be dependent on IL-2 and accessory cell IL-12 and IL-18 production and on cell-cell contact.…”