title: Experimental Trypanosoma cruzi infection in platelet-activating factor receptor-deficient mice.
abstract: The generation of an inflammatory response driven by Trypanosoma cruzi or its subproducts appears to be essential for tissue injury and disease pathogenesis. However, this inflammatory response is also relevant in the control of T. cruzi replication. The lipid mediator platelet-activating factor (PAF) has been implicated in a number of pathological conditions characterized by tissue inflammation. In the present study, we aimed at evaluating the role of PAF during T. cruzi infection by using mice that were genetically deficient in the PAF receptor. We observed that infected hearts of PAFR(-/-) mice had an increased number of parasite nests, associated with a more intense inflammatory infiltrate. This was associated with greater parasitemia and lethality. When wild-type and PAFR(-/-) mice were compared, there were no marked changes in the kinetics of the expression of MCP-1, RANTES, IFN-gamma and TNF-alpha in heart tissue of infected animals. Moreover, serum concentrations of TNF-alpha, nitrate and parasite-specific IgM were similar in both groups of mice. In vitro, macrophages from PAFR(-/-) animals did not phagocytose trypomastigote forms when activated with PAF, leukotriene B(4) or MCP-1 and produced less nitric oxide when infected and activated with IFN-gamma. These results are consistent with the hypothesis that endogenous synthesis of PAF and activation of PAF receptors control T. cruzi replication in mice in great part via facilitation of the uptake of the parasite and consequent activation of macrophages.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Talvani
authors.forename: Gilcinea
authors.initials: G
authors.lastname: Santana
authors.forename: Lucíola S
authors.initials: LS
authors.lastname: Barcelos
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Romanha
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000096:biosynthesis; D005260:Female; D006321:Heart / Q000469:parasitology; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood; D018512:Parasitemia; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D014349:Trypanosoma cruzi / Q000254:growth & development* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000913:Antibodies, Protozoan; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007075:Immunoglobulin M; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D007975:Leukotriene B4; D009569:Nitric Oxide; D007371:Interferon-gamma