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.
BACKGROUND
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.


RESULTS
We report here that engagement of TLR2 on DCs increases HIV-1 transmission toward CD4+ T cells by primarily affecting de novo 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.


CONCLUSIONS
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.
Thibault
Sandra
S
Faculté de Médecine, Université Laval, Québec, Canada. sandra.thibault@crchul.ulaval.ca
Fromentin
Rémi
R
Tardif
Mélanie R
MR
Tremblay
Michel J
MJ
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D003713:Dendritic Cells / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014779:Virus Replication
D007370:Interferon Type I; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4