The HTLV-I p30 interferes with TLR4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages

Abhik Datta, Uma Sinha-Datta, Navneet Kaur Dhillon, Shilpa Buch, Christophe Nicot

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Whereas adaptive immunity has been extensively studied, very little is known about the innate immunity of the host to HTLV-I infection. HTLV-I-infected ATL patients have pronounced immunodeficiency associated with frequent opportunistic infections, and in these patients, concurrent infections with bacteria and/or parasites are known to increase risks of progression to ATL. The Toll-like receptor-4 (TLR4) activation in response to bacterial infection is essential for dendritic cell maturation and links the innate and adaptive immune responses. Recent reports indicate that TLR4 is targeted by viruses such as RSV, HCV, and MMTV. Here we report that HTLV-I has also evolved a protein that interferes with TLR4 signaling; p30 interacts with and inhibits the DNA binding and transcription activity of PU.1 resulting in the down-regulation of the TLR4 expression from the cell surface. Expression of p30 hampers the release of pro-inflammatory cytokines MCP-1, TNF-α, and IL-8 and stimulates release of anti-inflammatory IL-10 following stimulation of TLR4 in human macrophage. Finally, we found that p30 increases phosphorylation and inactivation of GSK3-β a key step for IL-10 production. Our study suggests a novel function of p30, which may instigate immune tolerance by reducing activation of adaptive immunity in ATL patients.

Original languageEnglish (US)
Pages (from-to)23414-23424
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number33
DOIs
StatePublished - Aug 18 2006

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Toll-Like Receptor 4
Human T-lymphotropic virus 1
Macrophages
Adaptive Immunity
Anti-Inflammatory Agents
Cytokines
Innate Immunity
Interleukin-10
HTLV-I Infections
Immune Tolerance
Chemical activation
Opportunistic Infections
Interleukin-8
Bacterial Infections
Phosphorylation
Dendritic Cells
Transcription
Parasites
Viruses
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The HTLV-I p30 interferes with TLR4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages. / Datta, Abhik; Sinha-Datta, Uma; Dhillon, Navneet Kaur; Buch, Shilpa; Nicot, Christophe.

In: Journal of Biological Chemistry, Vol. 281, No. 33, 18.08.2006, p. 23414-23424.

Research output: Contribution to journalArticle

Datta, Abhik ; Sinha-Datta, Uma ; Dhillon, Navneet Kaur ; Buch, Shilpa ; Nicot, Christophe. / The HTLV-I p30 interferes with TLR4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 33. pp. 23414-23424.
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