TLR2 and TLR4 triggering exerts contrasting effects with regard to HIV-1 infection of human dendritic cells and subsequent virus transfer to CD4+ T cells

Abstract

<p>Abstract</p> <p>Background</p> <p>Recognition of microbial products through Toll-like receptors (TLRs) initiates inflammatory responses orchestrated by innate immune cells such as dendritic cells (DCs). As these cells are patrolling mucosal surfaces, a portal of entry for various pathogens including human immunodeficiency virus type-1 (HIV-1), we investigated the impact of TLR stimulation on productive HIV-1 infection of DCs and viral spreading to CD4⁺T cells.</p> <p>Results</p> <p>We report here that engagement of TLR2 on DCs increases HIV-1 transmission toward CD4⁺T cells by primarily affecting <it>de novo </it>virus production by DCs. No noticeable and consistent effect was observed following engagement of TLR5, 7 and 9. Additional studies indicated that both HIV-1 infection of DCs and DC-mediated virus transmission to CD4⁺T cells were reduced upon TLR4 triggering due to secretion of type-I interferons.</p> <p>Conclusion</p> <p>It can thus be proposed that exposure of DCs to TLR2-binding bacterial constituents derived, for example, from pathogens causing sexually transmissible infections, might influence the process of DC-mediated viral dissemination, a phenomenon that might contribute to a more rapid disease progression.</p