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Biology Articles » Immunobiology » Interactions Between Natural Killer Cells, Cortisol and Prolactin in Malaria During Pregnancy » NK Cells and Malaria

NK Cells and Malaria
- Interactions Between Natural Killer Cells, Cortisol and Prolactin in Malaria During Pregnancy

In P. falciparum infection, disease occurs only as a result of the asexual blood stage after the parasite leaves the liver and begins to invade and grow inside red blood cells. Important insight into the role of NK cells in immunity to malaria was provided on IL-12-related mechanisms in early stages of the disease in the model.42 Indeed, infection of mice can be ameliorated by administration of IL-12 early in the course of the infection. Untreated mice died 12 days after infection, while IL-12 treated mice survived. Administration of IL-12 early in the course of the disease improves the outcome of the infection in normal mice, leading to the development of IFN-γ, TNF-α and nitric oxide-dependent immunity.43 The role of nitric oxide was investigated by the administration of aminoguanidine, a selective inhibitor of cytokine inducible nitric oxide synthetase. Significantly increased mortality was observed following treatment twice daily with 9 mg of aminoguanidine, but there was no effect on parasitemia. Furthermore, in vivo depletion of NK cells after anti-GM1 antibody treatment results in a severely increased pathology, and IL-12-treated but NK cell-depleted A/J mice fully fail to control the infection.44 More recently, the role of NK cells in control of human malaria has begun to be investigated. Artavanis-Tsakonas and Riley46 have revealed that, in non-immune donors, NK cells are among the first cells in peripheral blood to produce IFN-γ in response to P. falciparum-infected red blood cells. In this setting, the authors observed that NK cells are activated during the first 18 hours of exposure to parasitized erythrocytes. This activation was dependent on IL-12 and also to a lesser extent on IL-18. Interestingly, cells from semi-immune African adults produce less IFN-γ, which might reflect haplotypic variation in KIR genotype among individuals and/or extensive functional allelic polymorphisms in KIR and toll like receptors.4648 These results were obtained with whole blood cells. Using purified cells, we have recently shown that NK cells from nonimmune individuals can kill plasmodia-infected erythrocytes in the absence of opsonizing antibodies directly through cell-cell interaction and that this activity was inhibited by anti-Fas antibody and granzyme B inhibitor.49 We also provide evidence that purified NK cells can inhibit growth of Plasmodia-infected erythrocytes opsonized with antibody from semi-immune African adults by around 25%, and that pre-treatment of NK cells with anti-Fas and granzyme B inhibitor prevents this growth inhibition.49


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