title: Evidence for a perforin-mediated mechanism controlling cardiac inflammation in Trypanosoma cruzi infection.
abstract: CD8+ T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (-/-) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (+/+) and (-/-) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8+ cells, was more evident in perforin (-/-) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (-/-) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (+/+) and (-/-) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi.
authors.affiliation: Laboratório de Biologia Celular - DUBC - Instituto Oswaldo Cruz FIOCRUZ, Rio de Janeiro, Brazil. andreah@ioc.fiocruz.br
authors.forename: Andrea
authors.initials: A
authors.lastname: Henriques-Pons
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Oliveira
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Paiva
authors.forename: Alexandre F S
authors.initials: AF
authors.lastname: Correa
authors.forename: Marcos M
authors.initials: MM
authors.lastname: Batista
authors.forename: Rodrigo C
authors.initials: RC
authors.lastname: Bisaggio
authors.forename: Chau-Ching
authors.initials: CC
authors.lastname: Liu
authors.forename: Vinicius
authors.initials: V
authors.lastname: Cotta-De-Almeida
authors.forename: Claudia M L M
authors.initials: CM
authors.lastname: Coutinho
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Persechini
authors.forename: Tania C
authors.initials: TC
authors.lastname: Araujo-Jorge
mesh_terms: D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000648:ultrastructure; D018512:Parasitemia / Q000276:immunology; D054353:Perforin; D005082:Physical Exertion; D052899:Pore Forming Cytotoxic Proteins; D014349:Trypanosoma cruzi
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma