Abstract
Natural killer (NK) cells are known to be activated during malaria infection, exhibiting both cytokine production and cytotoxic functions. However, NK cells are heterogeneous in their expression of surface activatory and inhibitory receptors which may influence their response to malaria parasites. Here, we studied the surface marker profile and activation dynamics of NK cells during a Controlled Human Malaria Infection in 12 healthy volunteers. Although there was significant inter-patient variability in timing and magnitude of NK cell activation, we found a consistent and strong increase in expression of the activatory receptor NKp30. Moreover, high baseline NKp30 expression was associated with NK cell activation at lower parasite densities. Our data suggest that NKp30 expression may influence the NK cell response to P. falciparum, explaining inter-patient heterogeneity and suggesting a functional role for this receptor in malaria.
Highlights
Malaria infection in humans activates a broad cellular immune response involving monocytes, T cells, B cells, and Natural killer (NK) cells
As there appears to be little activation of the CD56bright NK cell subset during the course of infection, we wanted to determine the ability of both the CD56brightCD16– and CD56dimCD16+ subsets to produce granzyme B and IFN-γ and degranulate during infection, using isolated and cryopreserved peripheral blood mononuclear cells (PBMCs) from study #2 (Supplementary Figure 3). We found that both subsets increase production of granzyme B and IFN-γ and show improved degranulation during infection (Figures 4A–C; Supplementary Figure 4). These data show that NKp30 is a marker for the NK cell response during a Controlled Human Malaria Infection, and suggests a possible functional role in the response to infected red blood cells
We demonstrate that the expression of this receptor at baseline relates to individual NK cell responses to P. falciparum in vivo
Summary
Malaria infection in humans activates a broad cellular immune response involving monocytes, T cells, B cells, and NK cells. During the pathological blood stage of P. falciparum infection, circulating NK cells display a dual functional role, i.e., cytokine production [2,3,4,5] and killing of infected blood cells both via antibody-independent [6,7,8] and antibody-dependent cytotoxicity [9, 10]. Their relative contribution to protection remains unknown. We hypothesized that this heterogeneity might at least in part be explained by differences in NK cell phenotype prior to infection
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