Interplay between hiv-1 and toll-like receptors in human myeloid cells: Friend or foe in hiv-1 pathogenesis?

The Toll-like receptors are the first line of the host response to pathogens, representing an essential com- ponent of the innate and adaptive immune response. They recognize different pathogens and trigger re- sponses directed at eliminating the invader and at de- veloping immunologic long-term memory, ultimately affecting viral pathogenesis. In viral infections, sensing of nucleic acids and/or viral structural proteins generally induces a protective immune response. Thus, it is not surprising that many viruses have developed strategies to evade or counteract signaling through the Toll-like receptor pathways, to survive the host defense machin- ery and ensure propagation. Thus, Toll-like receptor engagement can also be part of viral pathogenic mech- anisms. Evidence for a direct interaction of Toll-like receptors with human immunodeficiency virus type 1 (HIV-1) structures has started to be achieved, and alterations of their expression and function have been described in HIV-1–positive subjects. Furthermore, Toll- like receptor triggering by bacterial and viral ligands have been described to modulate HIV-1 replication and host response, leading to protective or detrimental effects. This review covers major advances in the field of HIV-1 interplay with Toll-like receptors, focusing on human myeloid cells (e.g., monocytes/macrophages and den- dritic cells). The role of this interaction in the dysregula- tion of myeloid cell function and in dictating aspects of the multifaceted pathogenesis of acquired immunodefi- ciency syndrome will be discussed