NDLI: Increased Trypanosoma cruzi Invasion and Heart Fibrosis Associated with High Transforming Growth Factor β Levels in Mice Deficient in α2-Macroglobulin

Content Provider	PubMed Central
Author	Waghabi, M. C. Coutinho, C. M. L. M. Soeiro, M. N. C. Pereira, M. C. S. Feige, J. J. Keramidas, M. Cosson, A. Minoprio, P. Leuven, F. Van Araújo-jorge, T. C.
Copyright Year	2002
Abstract	Trypanosoma cruzi proteinases are involved in host cell invasion in human patients and in mouse models. In mice, murine α2-macroglobulin (MAM) and murinoglobulin are circulating plasma proteinase inhibitors that also have important roles in inflammation and immune modulation. To define their role in experimental Chagas disease, we investigated the susceptibility to T. cruzi infection of mice that are deficient only in α2-macroglobulins (AM-KO) or in both MAM and monomeric murinoglobulin-1 (MM-KO), relative to the wild type (WT). Despite the high parasite load, parasitemia was lower in AM-KO and MM-KO mice than in WT mice. Nevertheless, we observed a significantly higher parasite load in the hearts of AM-KO and MM-KO mice, i.e., more amastigote nests and inflammatory infiltrates than in WT mice. This result demonstrates a protective role for MAM in the acute phase of murine T. cruzi infection. We further demonstrated in vitro that human α2-macroglobulins altered the trypomastigote morphology and motility in a dose-dependent way, and that also impaired T. cruzi invasion in cardiomyocytes. Finally, we demonstrated that the levels of transforming growth factor β in AM-KO mice increased significantly in the third week postinfection, concomitant with high amastigote burden and important fibrosis. Combined, these in vivo and in vitro findings demonstrate that the MAM contribute to the resistance of mice to acute myocarditis induced by experimental T. cruzi infection.
Related Links	http://dx.doi.org/10.1128/iai.70.9.5115-5123.2002
Ending Page	5123
Page Count	9
Starting Page	5115
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	9
Volume Number	70
Language	English
Publisher	American Society for Microbiology
Publisher Date	2002-09-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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