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

Medeiros MM, Peixoto JR, Oliveira AC, Cardilo-Reis L, Koatz VL, Van Kaer L, Previato JO, Mendonça-Previato L, Nobrega A, Bellio M
J Leukoc Biol. 2007 82 (3): 488-96

PMID: 17540734 · DOI:10.1189/jlb.0706478

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-1beta acts downstream of TNF-alpha, and a second, which is IL-1beta- and TNFRI-independent. Moreover, NKT cells participate in this proinflammatory cascade, as in GIPL-treated CD1d(-/-) mice, TNF-alpha 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 gammadelta+ T cells, it is not required for increasing CD69 expression on alphabeta+ 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.

MeSH Terms (24)

Animals Antigens, CD1 Antigens, CD1d Chemokine CXCL2 Chemokines Enzyme-Linked Immunosorbent Assay Flow Cytometry Glycolipids Immunity, Innate Inflammation Mediators Interleukin-1beta Lymphocyte Activation Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Neutrophil Infiltration Phospholipids Receptors, Tumor Necrosis Factor, Type I RNA, Messenger T-Lymphocytes Toll-Like Receptor 4 Trypanosoma cruzi Tumor Necrosis Factor-alpha

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