Association of TLR Gene Polymorphisms with Susceptibility to Visceral Leishmaniasis

Abstract

Leishmania donovani and Leishmania infantum are the two most important organisms that together are responsible for causing visceral leishmaniasis (VL). VL continues to be a significant public health burden; particularly in areas where there is a recognized endemicity for this disease. The response of the immune system by the host is critical in determining whether one will get infected or not. Toll-like receptors (TLRs), as a component of the innate immune response, detect the presence of pathogens by recognizing specific molecules and starting the sequence of events that provides the host with a defense against the pathogens they encounter. Genetic differences between people that occur at the level of the genes encoding proteins that are located within TLRs may be one of the many factors that affect whether or not a person becomes infected with a pathogen, such as VL.

This research has calculated the correlation of some selected TLR gene polymorphisms (TLR2, TLR4 and TLR9) with susceptibility to visceral leishmaniasis. The study design was a case-control study consisting of 120 VL patients with confirmed diagnosis compared with 120 healthy individuals. PCR-RFLP techniques were used for genotyping. The analytical methods used included; comparison of genotype frequencies, estimating odds ratios, and conducting one-way analyses of variance (ANOVA) to determine if there were any differences in immunologic markers.

Our findings suggest that there was a significant relationship between the polymorphism of TLR4 (Asp299Gly) and increased susceptibility to VL (p < 0.01). The parasite burden of those with the mutant allele were statistically significantly (p < 0.01) higher (average of 3.8 + 0.9 log parasites/mL) than the parasite load of those with the wild-type allele (average of 2.1 + 0.7 log parasites/mL). The polymorphism of TLR2 (Arg753Gln) also was moderately associated with susceptibility to VL (p < 0.05), while TLR9 polymorphism did not demonstrate any statistically significant association with susceptibility to VL (p > 0.05). ANOVA analysis revealed that cytokine concentrations differed significantly among genotype groups (p<0.001; F-value = 45.30), suggesting that TLR polymorphisms may influence how immune responses are regulated. Genetic variations in TLR genes may impact a person’s risk for developing visceral leishmaniasis (VL), potentially affecting how their immune system responds to other parasitic diseases. This information may help in identifying those who are at risk for developing VL and may also help inform the development of new therapies specific to individuals affected by VL.