Toll-like receptors genes and risk of latent tuberculosis infection in HIV-1 infected people

The purpose of this study was to determine the contribution of genetic factors, i.e. level of expression and polymorphisms of Toll-like receptors to the susceptibility of latent tuberculosis infection in Russian HIV-infected cohort. The patients (n=317) with confirmed HIV infection were divided into two groups according to the results of Standard E TB-Feron test: 63 cases having a latent TB infection and 274 controls without LTBI. Total DNA and RNA was isolated from whole blood samples. SNP genotyping and expression levels of five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR8) were determined by means of real-time PCR. There were no significant differences in the expression levels of TLRs between case and control groups. In addition, we did not observe any significant association of the analyzed SNPs with the susceptibility of LTBI in HIV-patients. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes are characterised by lower CD4 T-cells count compared to carriers of alternative alleles. Moreover, we found significant risk of CD4 T-cells count hazardous drop below 350 cells/mm3 associated with rs4986790-G (TLR4) allele. Latent tuberculosis infection in HIV-infected individuals does not significantly modify the level of TLR gene expression.