Polymorphisms of the KIR Genes Complex and Ligands Associated with the Dynamics of Plasmodium vivax Infection in Brazilian Amazon Basin

The resistance to infection and the heterogeneity of clinical signs depend on several factors, being noteworthy host genetic factors. In this context the immune response, in particular innate immunity, plays a central role in this process, especially natural killer (NK) cells, which act early against intracellular pathogens. Killer cell imunoglobulin-like receptors (KIR) are expressed on the surface of NK cells and modulate their function, inhibiting or activating them through the interaction with HLA class I ligands expressed in the target cells. This study was undertaken to evaluate the role of KIR genes/ligands polymorphisms in the predisposition to infection by P. vivax and association with infections parameters like parasitaemia and gametocytes counting. Fourteen KIR genes and their ligands were genotyped on 62 Plasmodium vivax infected and 83 uninfected individuals living in the locality of Goianesia of Para (infection defined clinically and by thick smear). The KIR genes were genotyped by PCR-SSP followed by acrylamide gel electrophoresis and silver nitrate staining. The HLA-C ligands were genotyped by real time PCR. Among the 14 KIR genes, the findings showed the association of KIR2DL5 and KIR2DS5 genes with P. vivax infection and the genes KIR3DS1 and KIR2DS1 were associated with increasing in the parasitaemia and with increased counting of gametocytes in infected by P. vivax, respectively (Mann-Whitney test; p=0.01). Moreover, KIR3DS1 presence associates with P. vivax CSP multiple genotypes (Fisher Exact test; p=0.0084). Interestingly, individuals presenting multiple genotypes of P. vivax CSP showed also higher parasitaemia (Mann-Whitney test; p=0.028). Fulfilling this scenario IL-17 concentration correlated negatively with parasitaemia (r=-0.6702; p=0.024), suggesting a protective role in the parasitaemia control. Noteworthy, KIR3DS1 is a key stimulatory receptor of Natural Killer cells that produces many cytokines related to immune response to P. vivax infection being the results suggestive of a role of this gene in control of the number of different circulating CSP genotypes as well as parasitaemia and highlights KIR3DS1 role’s in malaria immune response in Brazilian Amazon Basin population.