Toll-like receptors, cytokines and HIV-1

The present investigation examined variations in cytokine and Toll-like receptor expression by T-lymphocytes in HIV infection. 50 HIV cases and 10 normal controls were evaluated for TLR3, TLR4, TLR8, TLR9, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-alpha, and IFN-gamma expression and staining intensities. TLR3 was expressed in 37 HIV (74%) cases, and TLR4 was brightly expressed in all (100%) HIV cases. However, TLR3 and TLR4 remained negative in all normal controls. Results reveal that TLR4 up-regulation is not limited to gram-negative bacterial infection. No statistical difference was detected when TLR8 and TLR9 expression were compared between the two test populations. A statistically significant difference was detected when IL-2, IL-4, IL-6, IL-10, IL-12, and IFN-gamma expression were analyzed in HIV cases and normal controls. When cytokine expression was compared with stage of disease, results indicated that a Th(1) to Th(2) cytokine switch did not occur. Only TNF-alpha expression decreased as infection progressed from the chronic phase into AIDS. When TLR expression was compared to cytokine expression, no statistical differences were detected. These data point to the need for a more in-depth study to determine whether or not the up-regulation of Toll-like receptor expression increases cytokine expression via the NFkappaB pathway.