title: Mast cell function and death in Trypanosoma cruzi infection.
abstract: Although the roles of mast cells (MCs) are essential in many inflammatory and fibrotic diseases, their role in Trypanosoma cruzi-induced cardiomyopathy is unexplored. In this study, we treated infected CBA mice with cromolyn, an MC stabilizer, and observed much greater parasitemia and interferon-γ levels, higher mortality, myocarditis, and cardiac damage. Although these data show that MCs are important in controlling acute infection, we observed MC apoptosis in the cardiac tissue and peritoneal cavity of untreated mice. In the heart, pericardial mucosal MC die, perhaps because of reduced amounts of local stem cell factor. Using RT-PCR in purified cardiac MCs, we observed that infection induced transcription of P2X(7) receptor and Fas, two molecules reportedly involved in cell death and inflammatory regulation. In gld/gld mice (FasL(-/-)), apoptosis of cardiac, but not peritoneal, MCs was decreased. Conversely, infection of P2X(7)(-/-) mice led to reduced peritoneal, but not cardiac, MC death. These data illustrate the immunomodulatory role played by MCs in T. cruzi infection and the complexity of molecular interactions that control inflammatory pathways in different tissues and compartments.
authors.affiliation: Laboratório de Inovações em Terapias, Ensino, e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. meuser@ioc.fiocruz.br
authors.forename: Marcelo
authors.initials: M
authors.lastname: Meuser-Batista
authors.forename: José Raimundo
authors.initials: JR
authors.lastname: Corrêa
authors.forename: Vinícius Frias
authors.initials: VF
authors.lastname: Carvalho
authors.forename: Constança Felícia De Paoli
authors.initials: CF
authors.lastname: de Carvalho Britto
authors.forename: Otacilio da Cruz
authors.initials: OC
authors.lastname: Moreira
authors.forename: Marcos Meuser
authors.initials: MM
authors.lastname: Batista
authors.forename: Maurílio José
authors.initials: MJ
authors.lastname: Soares
authors.forename: Francisco Alves Farias
authors.initials: FA
authors.lastname: Filho
authors.forename: Patrícia Machado R
authors.initials: PM
authors.lastname: E Silva
authors.forename: Joseli
authors.initials: J
authors.lastname: Lannes-Vieira
authors.forename: Robson Coutinho
authors.initials: RC
authors.lastname: Silva
authors.forename: Andrea
authors.initials: A
authors.lastname: Henriques-Pons
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D014355:Chagas Disease / Q000469:parasitology* / Q000473:pathology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000469:parasitology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D007377:Interleukin-3; D058486:Receptors, Purinergic P2X7; D019089:Stem Cell Factor; D019014:fas Receptor; D004205:Cromolyn Sodium