Expression of Toll-like Receptors and Chemokine Receptors in the Early and Advanced Stages of HIV Infection Aggravated by Mycobacterium tuberculosis

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Abstract
This study examined Toll-like receptors (TLRs)/chemokine receptors (CCRs) gene expression levels in HIV-infected individuals at different stages of HIV infection. It has been demonstrated that in the advanced stages of HIV infection, aggravated by Mycobacterium tuberculosis (M. tuberculosis) infection, there was a significant increase in TLR2, TLR4, TLR7, and TLR9 expression levels (181-, 8.4-, 15-, and 3.4-fold, respectively), compared to the early stages of the disease, which also correlated with an increase in viral load. The advanced stages of HIV infection were also characterized by an increased CCR5 expression level (8.08-fold, p < 0.0001) on patients’ mononuclear cells, which was not observed in the early stages of the disease. A positive correlation was found between the enhanced levels of TLR2/TLR4 and CCR5 expression, which facilitates the entry of HIV-1 into the cell (r = 0.03564, p = 0.0423 for TLR2/TLR4; r = 0.3793, p = 0.0269 for CCR5). The advanced stages of HIV infection were characterized by a sharp increase in the expression levels of CXCR4 and CCR8 co-receptors which also play an important role in the entry of HIV-1 into the host cell (more than 537-fold, p = 0.0006, and 5000-fold, p = 0.004, respectively). At the advanced stages of HIV infection, a positive correlation was found between increased production of TLR and CCR and elevated expression of IL-12 and IL-18. These factors contribute to virus persistence and chronic immune activation observed in patients with opportunistic infections. Thus, the obtained data indicate that HIV-1 in the advanced stages of infection induces an increased TLRs and CCRs expression, which, together with enhanced viral production, leads to chronic inflammation and can contribute to tissue damage and exacerbate the disease’s progression.

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