HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-alpha 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-alpha 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-alpha 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-alpha) and the immunosuppressive cytokine IL-10 both involved in immune dysregulation during early HIV-1 infection and AIDS progression.
keyword : HIV-1 TLR4 Tat IL-10 TNF-α
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Article dans une revue
Retrovirology, BioMed Central, 2013, 10 (1), pp.123. 〈10.1186/1742-4690-10-123〉
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Soumis le : mardi 10 décembre 2013 - 17:01:12
Dernière modification le : jeudi 11 janvier 2018 - 06:23:24
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Nawal Ben Haij, Kaoutar Leghmari, Rémi Planès, Nathalie Thieblemont, Elmostafa Bahraoui. HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-alpha and IL-10.. Retrovirology, BioMed Central, 2013, 10 (1), pp.123. 〈10.1186/1742-4690-10-123〉. 〈inserm-00916791〉

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