title: HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-α and IL-10.
abstract: BACKGROUND
  HIV-1 infection results in hyper-immune activation and immunological disorders as early as the asymptomatic stage. Here, we hypothesized that during early HIV-1 infection, HIV-1 Tat protein acts on monocytes/macrophages to induce anti-inflammatory and proinflammatory cytokines and participates in immune dysregulation.
  
  
  RESULTS
  In this work we showed that Tat protein: i) by its N-terminal domain induces production of both IL-10 and TNF-α in a TLR4-MD2 dependent manner, ii) interacts specifically with TLR4-MD2 and MD2 with high affinity but not with CD14, iii) induces in vivo TNF-α and IL-10 in a TLR4 dependent manner.
  
  
  CONCLUSIONS
  Collectively, our data showed for the first time that, HIV-1 Tat interacts physically with high affinity with TLR4-MD2 to promote proinflammatory cytokines (TNF-α) and the immunosuppressive cytokine IL-10 both involved in immune dysregulation during early HIV-1 infection and AIDS progression.
authors.affiliation: Université Paul Sabatier, EA 3038, 118 Route de Narbonne, 31062 Toulouse, France. bahraoui@cict.fr.
authors.forename: Nawal
authors.initials: N
authors.lastname: Ben Haij
authors.forename: Kaoutar
authors.initials: K
authors.lastname: Leghmari
authors.forename: Rémi
authors.initials: R
authors.lastname: Planès
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thieblemont
authors.forename: Elmostafa
authors.initials: E
authors.lastname: Bahraoui
mesh_terms: D002478:Cells, Cultured; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*
chemical_list: C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10