Role of translocated bacterial flagellin in monocyte activation among individuals with chronic HIV-1 infection

Abstract

Monocyte activation has been identified as a predictor of mortality and morbidity in HIV-1 infection. This study investigated translocated bacterial flagellin as a potential contributor to systemic monocyte activation via Toll-like receptor 5 (TLR5) stimulation.We demonstrated that circulating flagellin correlated to anti-flagellin, which was associated with soluble markers of microbial translocation (LPS, LBP) and monocyte activation (sCD14, sCD163). Flagellin exposure in vitro reduced monocyte TLR5 expression and the magnitude of reduction was correlated to anti-flagellin levels, indicative of previous flagellin exposure. Circulating anti-flagellin and basal TLR5 expression were both associated with basal and flagellin-stimulated monocyte cytokine production, where HIV+ and HIV− differed in their cytokine patterns (IL-1β, IL-6, IL-8).Our results suggest that translocated flagellin contributes to systemic immune activation in HIV-1 infection and reduces monocyte surface TLR5 expression resulting in a hyperactivated state with elevated basal cytokine production and reduced ability to respond to further TLR5 stimulation.