HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-α and IL-10Reportar como inadecuado




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Retrovirology

, 10:123

First Online: 28 October 2013Received: 03 July 2013Accepted: 09 October 2013

Abstract

BackgroundHIV-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.

ResultsIn 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.

ConclusionsCollectively, 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.

KeywordsHIV-1 TLR4 Tat IL-10 TNF-α Electronic supplementary materialThe online version of this article doi:10.1186-1742-4690-10-123 contains supplementary material, which is available to authorized users.

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Autor: Nawal Ben Haij - Kaoutar Leghmari - Rémi Planès - Nathalie Thieblemont - Elmostafa Bahraoui

Fuente: https://link.springer.com/







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