Open Access“Autoimmune rejection” of neonatal heart transplants in experimental Chagas disease is a parasite-specific response to infected host tissue
Author(s) -
Rick L. Tarleton,
L. Zhang,
M O Downs
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.8.3932
Subject(s) - chagas disease , trypanosoma cruzi , immunology , biology , inflammation , immune system , myocarditis , parasite hosting , medicine , world wide web , computer science
Infection with the protozoan parasiteTrypanosoma cruzi often results in chronic heart- and gut-associated disease known as Chagas disease. In this study we show that contrary to previous reports, neonatal hearts transplanted into mice chronically infected withT. cruzi do not exhibit signs of autoimmune-type rejection or any significant inflammatory response. In addition to an absence of inflammation, these syngeneic heart transplants survive for more than 1 year and are absolutely free of parasites as determined byin situ PCR analysis. However, if well-established transplanted hearts in chronically infected mice are directly injected with live parasites, a rapid and dramatic inflammatory response ensues that results in cessation of heart function. Likewise, transplanted hearts established in mice prior to systemic infection withT. cruzi or hearts transplanted into mice during the acute stage ofT. cruzi infection become parasitized and develop inflammatory foci. In these cases where the transplanted hearts become parasitized, the ensuing inflammatory response is nearly identical to that observed in the native hearts ofT. cruzi -infected mice in terms of cell types present and adhesion molecules and cytokines expressed. Importantly, this response is strikingly different from that observed in the allogeneic heart rejection. These results clearly document that parasitization of heart tissue is both necessary and sufficient for the induction of tissue damage in Chagas disease and strongly argue against a principal autoimmune etiology for this disease.