Wenqing Geng, Sha Li, Xueji
Background: Deficient interferon (IFN)-α production of plasmacytoid DCs (pDCs) from HIV-1-infected individuals in response to virus or toll-like receptor (TLR) stimulation has been reported. pDCs express TLR7 and TLR9, but whether and how the TLR pathway contributes to the deficiency has not been well addressed. Methods: Twenty-six subjects with HIV-1 infection were recruited from a chronic HIV-1 infection (CHI) cohort of men who have sex with men (MSM) and 15 HIV-1 negative healthy MSM were used as normal controls (NCs). Maturation markers (CD80, CD86, CD83, CD40, CCR7), TLR7 and TLR9, nuclear factor κB (NF-κB) and interferon regulatory factor 7 (IRF7) expression were detected using surface and intracellular multicolor flow cytometry. Intracellular IFN-α production of pDCs was measured in response to R848 (TLR7 agonist) and ODN2216 (TLR9 agonist), respectively. Results: IFN-α production of pDCs with treatment of R848, but not ODN2216, from MSM with CHI was significantly lower than that of NCs. There was no significant difference in maturation marker expression between MSM with CHI and NCs. The expression of TLR7 and TLR9 on pDCs of MSM with CHI was significantly up-regulated. The expression of IRF7, a downstream signaling protein in the TLR7/9 signaling pathway, was significantly down-regulated as compared with that of NCs. NF-κB expression of pDCs of MSM with CHI were similar to that of NCs. Conclusions: These results indicated that decreased IRF7 expression might contribute to deficient IFN-α production in MSM with CHI, suggesting efforts to increase the expression of IRF7 might resume the function of pDCs in individuals with CHI.