title: Dectin-1/TLR2 and NOD2 agonists render dendritic cells susceptible to infection by X4-using HIV-1 and promote cis-infection of CD4(+) T cells.
abstract: HIV-1 pathogenesis is intimately linked with microbial infections and innate immunity during all stages of the disease. While the impact of microbial-derived products in transmission of R5-using virus to CD4(+) T cells by dendritic cells (DCs) has been addressed before, very limited data are available on the effect of such compounds on DC-mediated dissemination of X4-tropic variant. Here, we provide evidence that treatment of DCs with dectin-1/TLR2 and NOD2 ligands increases cis-infection of autologous CD4(+) T cells by X4-using virus. This phenomenon is most likely associated with an enhanced permissiveness of DCs to productive infection with X4 virus, which is linked to increased surface expression of CXCR4 and the acquisition of a maturation profile by DCs. The ensuing DC maturation enhances susceptibility of CD4(+) T cells to productive infection with HIV-1. This study highlights the crucial role of DCs at different stages of HIV-1 infection and particularly in spreading of viral strains displaying a X4 phenotype.
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre Hospitalier Universitaire de Québec-Pavillon CHUL, Québec, Canada.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Côté
authors.forename: Audrey
authors.initials: A
authors.lastname: Plante
authors.forename: Mélanie R
authors.initials: MR
authors.lastname: Tardif
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D001426:Bacterial Proteins / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D002450:Cell Communication; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D005408:Flagellin / Q000494:pharmacology; D015870:Gene Expression; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D037181:Lectins, C-Type / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D056189:Viral Tropism / Q000187:drug effects / Q000502:physiology*; D000099181:Dectin-1
chemical_list: D001426:Bacterial Proteins; D005408:Flagellin; D037181:Lectins, C-Type; D055666:Lipopeptides; D008070:Lipopolysaccharides; D053473:Nod2 Signaling Adaptor Protein; D011070:Poly I-C; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D051195:Toll-Like Receptor 2; C584933:CCR5 protein, human; C546929:CLEC7A protein, human; D000099181:Dectin-1; C527276:CXCR4 protein, human; C429018:NOD2 protein, human; C508075:Pam(3)CSK(4) peptide; C495342:TLR2 protein, human