Genetic variability of molecules involved in the disease pathogenesis in Leishmania infection

Abstract

Macrophages are the primary host cell for Leishmania parasites, by Toll like receptors (TLR-MyD88) that are central components of the innate and adaptive immunity against leishmania infection. The CD40/CD40L interaction has also been shown to be important in resistance to various protozoa. In this context, one of the most important properties of suppressors of cytokine signalling (SOCS) proteins, especially SOCS1 and SOCS3, is the regulation of macrophages cell for Leishmania parasites. In the present study we evaluated variants of molecules involved in activation and modulation of leishmanicidal signaling cascades and the possible associations between polymorphisms present in the TLR2, TLR4, MyD88, CD40, SOCS1, SOCS3 genes with susceptibility/resistent to Leishmania. The results suggest the absence of any association between TLR2 and TLR4 variants and susceptibility to Leishmaniasis. Analysis of the nucleotide sequence encoding the TIR recognition domain of the MyD88 molecule showed that it is highly conserved when compared to the reference sequences. In contrast, heterozygous rs 12953258, which reflects a decrease in the expression of SOCS3, suggesting that it may be involved in the leishmaniasis susceptibility. This study is a first advance in the analysis of polymorphisms of genes involved in the signaling pathway of the macrophage and their relationship with leishmaniases infection and disease progression.

Keywords: Cytokine signalling; Host immune responses; Leishmania asymptomatic; Leishmania infection; Polymorphism.