| dc.description.abstract | Background: Chronic HIV-1 infection is characterized by high levels of persistent
immune activation. Both HIV-1-encoded Toll-like receptor 7/8 (TLR7/8) ligands and
TLR ligands encoded by products of microbial translocation have been implicated in
inducing and sustaining immune activation in infected individuals, but the consequences
of simultaneous exposure to different TLR ligands are not well understood.
Objective: To examine the impact of preexposure of monocytes to HIV-1-encoded
TLR8 ligands on their ability to respond to subsequent stimulation with microbial TLR2/
4 ligands.
Method: Stable monocytic cell lines (THP-1-Blue-CD14 cells) or primary monocytes
were stimulated with ligands for TLR2, TLR4, and TLR8, including chemically inactivated
HIV-1, alone, or in sequential combinations. Responses by THP-1 cells to TLR
stimulation were quantified using Quanti-Blue colometric assay, and TLR-induced
tumor necrosis factor-a production of primary monocytes was quantified by intracellular
cytokine staining using flow cytometry.
Results: The exposure of monocytes to HIV-1 or HIV-1-derived TLR8 ligands sensitized
these cells for TLR4 stimulation, resulting in a significantly higher response to lipopolysaccharide
compared to cells that were not prestimulated with TLR8 ligands or HIV-1.
Conclusion: TLR crosstalk can enhance the pro-inflammatory monocytes response to
products of microbial translocation and might play an important role in the modulation
of immune function in HIV-1 infection | en |
