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

Published online before print May 31, 2007

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0706478v1 82/3/488    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Medeiros, M. M. Articles by Bellio, M. Search for Related Content PubMed PubMed Citation Articles by Medeiros, M. M. Articles by Bellio, M.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0706478

Received for publication July 27, 2006.
Revised March 27, 2007.
Accepted for publication April 25, 2007.

Article

Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi

Monica M. Medeiros ^*, Jaqueline R. Peixoto ^*, Ana-Carolina Oliveira ^*, Larissa Cardilo-Reis , Vera L. G. Koatz , Luc Van Kaer , José O. Previato , Lúcia Mendonça-Previato , Alberto Nobrega ^*, and Maria Bellio ^*@

Institutos de *Microbiologia Prof. Paulo de Góes, Bioquímica Médica, and Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ) CCS, Cidade Universitária, Rio de Janeiro, RJ, Brazil; and Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

^@ To whom correspondence should be addressed. E-mail: belliom{at}acd.ufrj.br.

	Abstract

We have demonstrated recently that the glycoinositolphospholipid (GIPL) molecule from the protozoan Trypanosoma cruzi is a TLR4 agonist with proinflammatory effects. Here, we show that GIPL-induced neutrophil recruitment into the peritoneal cavity is mediated by at least two pathways: one, where IL-1 acts downstream of TNF-, and a second, which is IL-1- and TNFRI-independent. Moreover, NKT cells participate in this proinflammatory cascade, as in GIPL-treated CD1d^-/- mice, TNF- and MIP-2 levels are reduced significantly. As a consequence of this inflammatory response, spleen and lymph nodes of GIPL-treated mice have an increase in the percentage of T and B cells expressing the CD69 activation marker. Cell-transfer experiments demonstrate that T and B cell activation by GIPL is an indirect effect, which relies on the expression of TLR4 by other cell types. Moreover, although signaling through TNFRI contributes to the activation of B and ⁺ T cells, it is not required for increasing CD69 expression on ⁺ T lymphocytes. It is interesting that T cells are also functionally affected by GIPL treatment, as spleen cells from GIPL-injected mice show enhanced production of IL-4 following in vitro stimulation by anti-CD3. Together, these results contribute to the understanding of the inflammatory properties of the GIPL molecule, pointing to its potential role as a parasite-derived modulator of the immune response during T. cruzi infection.

Key Words: neutrophils • TNF- • IL-1 • T cells • CD69

This article has been cited by other articles:

				F. F. Tuon, V. S. Amato, H. A. Bacha, T. AlMusawi, M. I. Duarte, and V. Amato Neto Toll-Like Receptors and Leishmaniasis Infect. Immun., March 1, 2008; 76(3): 866 - 872. [Full Text] [PDF]