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HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-? 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-? 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-? 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-?) and the immunosuppressive cytokine IL-10 both involved in immune dysregulation during early HIV-1 infection and AIDS progression.

SUBMITTER: Ben Haij N

PROVIDER: S-EPMC4231456 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Ben Haij Nawal N Leghmari Kaoutar K Planès Rémi R Thieblemont Nathalie N Bahraoui Elmostafa E

Retrovirology 20131028

<h4>Background</h4>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.<h4>Results</h4>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 ...[more]

PMID: 24165011

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