title: Activation of Toll-like receptor 2 increases macrophage resistance to HIV-1 infection.
abstract: Patients infected with HIV-1, the etiological agent of AIDS, have increased intestinal permeability, which allows for the passage of microbial products, including Toll-like receptor (TLR) ligands, into circulation. The exposure of HIV-1-infected cells to certain TLR agonists affects viral replication, but studies associating viral production with the activation of TLR2 in HIV-1-infected cells are rare and controversial. Here, we report that the TLR2 ligands Zymosan and Pam3CSK4 potently inhibit HIV-1 replication in acutely infected monocyte-derived macrophages and the exposure to TLR2 ligands prior to infection renders macrophages refractory to HIV-1 production. Macrophage treatment with Pam3CSK4 did not change the cellular expression of the HIV-1 entry receptors CD4 and CCR5. Both TLR2 ligands increased the macrophage production of β-chemokines and IL-10, and the blockage of these soluble factors prevented the inhibitory effect of TLR2 activation on HIV-1 replication. Our findings show that the direct engagement of TLR2 in HIV-1-infected macrophages increase cellular resistance to HIV-1 infection, and that controlling HIV-1 replication with agonists for TLR2 might have implications for the development of antiretroviral therapies.
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Av. Brasil 4365, Manguinhos - 21040-360, Rio de Janeiro, RJ, Brazil.
authors.forename: Sabina
authors.initials: S
authors.lastname: Victoria
authors.forename: Jairo R
authors.initials: JR
authors.lastname: Temerozo
authors.forename: Livia
authors.initials: L
authors.lastname: Gobbo
authors.forename: Haynna K
authors.initials: HK
authors.lastname: Pimenta-Inada
authors.forename: Dumith Chequer
authors.initials: DC
authors.lastname: Bou-Habib
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014779:Virus Replication / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; C584933:CCR5 protein, human; D015704:CD4 Antigens; D018925:Chemokines; D008024:Ligands; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D019713:Receptors, CCR5; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D015054:Zymosan
keywords: AIDS; HIV; HIV-1; IL; IL-10; LPS; Macrophages; PAMP; PBMCs; PHA; TLR; Toll-like receptor; Toll-like receptors.; acquired immunodeficiency syndrome; human immunodeficiency virus type-1; interleukin; lipopolysaccharide; pathogen-associated molecular patterns; peripheral blood mononuclear cells; phytohemagglutinin; β-Chemokines