Toll-Like Receptor Genes and Risk of Latent Tuberculosis Infection in People Infected with HIV-1

Abstract

The purpose of this study was to determine the contribution of genetic factors, i.e., the level of expression and polymorphisms of Toll-like receptors (TLR), to the susceptibility of latent tuberculosis infection in a Russian cohort of individuals infected with HIV. The patients (n = 317) with confirmed HIV infection were divided into two groups according to the results of the STANDARD E TB-Feron test: 63 cases with a latent TB infection and 274 controls without LTBI. Total DNA and RNA were 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 the TLRs between the case and control groups. In addition, we did not observe any significant association between the analyzed SNPs and the susceptibility of Latent tuberculosis infection (LTBI) in patients with HIV. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes were characterized by lower CD4 T-cell counts compared to carriers of alternative alleles. Moreover, we found a significant risk of a hazardous drop in the CD4 T-cell count below 350 cells/mm3 associated with the rs4986790-G (TLR4) allele. Latent tuberculosis infection in individuals infected with HIV does not significantly modify the level of TLR gene expression.