Abstract
Natural killer (NK) cells have different roles in the host response against Plasmodium-induced malaria depending on the stage of infection. Liver NK cells have a protective role during the initial hepatic stage of infection by production of the TH1-type cytokines IFN-γ and TNF-α. In the subsequent erythrocytic stage of infection, NK cells also induce protection through Th1-type cytokines but, in addition, may also promote development of cerebral malaria via CXCR3-induction on CD8+ T cells resulting in migration of these cells to the brain. We have recently shown that the regulatory Ly49E NK receptor is expressed on liver NK cells in particular. The main objective of this study was therefore to examine the role of Ly49E expression in the immune response upon Plasmodium berghei ANKA infection, for which we compared wild type (WT) to Ly49E knockout (KO) mice. We show that the parasitemia was higher at the early stage, i.e. at days 6–7 of Plasmodium berghei ANKA infection in Ly49E KO mice, which correlated with lower induction of CD69, IFN-γ and TNF-α in DX5− liver NK cells at day 5 post-infection. At later stages, these differences faded. There was also no difference in the kinetics and the percentage of cerebral malaria development and in lymphocyte CXCR3 expression in WT versus Ly49E KO mice. Collectively, we show that the immune response against Plasmodium berghei ANKA infection is not drastically affected in Ly49E KO mice. Although NK cells play a crucial role in Plasmodium infection and Ly49E is highly expressed on liver NK cells, the Ly49E NK receptor only has a temporarily role in the immune control of this parasite.
Highlights
Malaria is a global disease that resulted in more than 650,000 deaths in 2010
As Natural killer (NK) cells play a crucial role in the immune response controlling Plasmodium infection [4,5,6], and as we have recently shown that murine liver NK cells express high levels of the Ly49E receptor [25], we hypothesized that Ly49E plays a regulatory role in the NK response during this infection
As Takeda et al [28] have shown that liver NK cells can be subdivided on the basis of DX5 expression, and as we have shown that Ly49E is preferentially expressed by DX52 liver NK cells [25], we compared the absolute number of DX52 and DX5+ liver NK cells in P. berghei ANKA-infected wild type (WT) vs Ly49E KO mice at days 5 and 7 p.i. (Figure 2A)
Summary
Malaria is a global disease that resulted in more than 650,000 deaths in 2010 (www.who.int). It is caused by protozoan Plasmodium parasites that are transmitted by infected Anopheles mosquitoes. A cyclic phase starts in which merozoites develop in the RBC as ring forms, followed by the progression to trophozoites and eventually to mature schizonts. Rupture of these schizonts and lysis of the RBCs results in release of a new wave of merozoites, which invade other RBCs [1,2,3]
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