TLR2 signaling renders quiescent naive and memory CD4+ T cells more susceptible to productive infection with X4 and R5 HIV-type 1.
It has been recently demonstrated that circulating microbial products are responsible for a systemic immune activation in individuals infected with HIV-type 1. Bacterial products carry structural conserved motifs recognized by TLRs. Some TLR members are expressed in primary human CD4+ T cells but the precise functional role played by these pattern recognition receptors is still imprecise. In this study, we report that engagement of TLR2 in quiescent naive and memory CD4+ T cells leads to the acquisition of an effector-like phenotype. Interestingly, engagement of TLR2 renders both cell subsets more susceptible to productive infection with X4 virions and a higher virus production was seen with R5 viruses. It can be proposed that exposure of resting CD4+ T cells to pathogen-derived products that can engage TLR2 induces the acquisition of an effector-like phenotype in naive and memory CD4+ T lymphocytes, a phenomenon that might result in an acceleration of virus replication, immune dysregulation, and HIV-type 1-mediated disease progression.
Thibault
Sandra
S
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Faculté de Médecine, Université Laval, Québec, Canada.
Tardif
Mélanie R
MR
Barat
Corinne
C
Tremblay
Michel J
MJ
D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002469:Cell Separation; D004198:Disease Susceptibility; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
D015415:Biomarkers; D016328:NF-kappa B; D019713:Receptors, CCR5; D051195:Toll-Like Receptor 2