HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 33, 23414-23424, August 18, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/33/23414    most recent M600684200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Datta, A. Articles by Nicot, C. Search for Related Content PubMed PubMed Citation Articles by Datta, A. Articles by Nicot, C. Social Bookmarking                      What's this?

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, and Christophe Nicot¹

From the Departments of Microbiology, Immunology, and Molecular Genetics and Pathology, University of Kansas Medical Center, Kansas City, Kansas 66160

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-, 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- 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.

Received for publication, January 23, 2006 , and in revised form, June 13, 2006.

^* This work was supported by Grants R01AI058944 and RR016443 (COBRE Program of the National Center for Research Resources) from the National Institutes of Health (to C. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: University of Kansas Medical Center, Dept. of Microbiology, Immunology, and Molecular Genetics, 3025 Wahl Hall W., 3901 Rainbow Blvd., Kansas City, KS 66160; E-mail: cnicot{at}kumc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?