HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-alpha and IL-10. - Archive ouverte HAL Access content directly
Journal Articles Retrovirology Year : 2013

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

(1, 2) , (1, 2) , (1, 2) , (3) , (1, 2)
1
2
3

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.
Fichier principal
Vignette du fichier
1742-4690-10-123.pdf (884 Ko) Télécharger le fichier
Vignette du fichier
1742-4690-10-123.xml (73.76 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Loading...

Dates and versions

inserm-00916791 , version 1 (10-12-2013)

Identifiers

Cite

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, 2013, 10 (1), pp.123. ⟨10.1186/1742-4690-10-123⟩. ⟨inserm-00916791⟩
210 View
255 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More