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Infection and Immunity, July 2007, p. 3641-3650, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00423-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Modulation of Autoimmunity by Treatment of an Infectious Disease{triangledown}

Kenneth V. Hyland,1 Juan S. Leon,2 Melvin D. Daniels,1 Nick Giafis,1 LaKitta M. Woods,1 Thomas J. Bahk,3 Kegiang Wang,1 and David M. Engman1*

Departments of Microbiology-Immunology and Pathology and Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois,1 Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia,2 Pediatric Critical Care of Arizona, Phoenix, Arizona3

Received 22 March 2007/ Returned for modification 16 April 2007/ Accepted 26 April 2007

Chagas’ heart disease (CHD), caused by the parasite Trypanosoma cruzi, is the most common form of myocarditis in Central America and South America. Some humans and experimental animals develop both humoral and cell-mediated cardiac-specific autoimmunity during infection. Benznidazole, a trypanocidal drug, is effective at reducing parasite load and decreasing the severity of myocarditis in acutely infected patients. We hypothesized that the magnitude of autoimmunity that develops following T. cruzi infection is directly proportional to the amount of damage caused by the parasite. To test this hypothesis, we used benznidazole to reduce the number of parasites in an experimental model of CHD and determined whether this treatment altered the autoimmune response. Infection of A/J mice with the Brazil strain of T. cruzi leads to the development of severe inflammation, fibrosis, necrosis, and parasitosis in the heart accompanied by vigorous cardiac myosin-specific delayed-type hypersensitivity (DTH) and antibody production at 21 days postinfection. Mice succumbed to infection within a month if left untreated. Treatment of infected mice with benznidazole eliminated mortality and decreased disease severity. Treatment also reduced cardiac myosin-specific DTH and antibody production. Reinfection of treated mice with a heart-derived, virulent strain of T. cruzi or immunization with myosin led to the redevelopment of myosin-specific autoimmune responses and inflammation. These results provide a direct link between the levels of T. cruzi and the presence of autoimmunity and suggest that elimination of the parasite may result in the reduction or elimination of autoimmunity in the chronic phase of infection.

* Corresponding author. Mailing address: Northwestern University, Department of Pathology, Ward Building 6-175, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-1288. Fax: (312) 503-1265. E-mail: d-engman{at}northwestern.edu

{triangledown} Published ahead of print on 7 May 2007.

Editor: W. A. Petri, Jr.

Infection and Immunity, July 2007, p. 3641-3650, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00423-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zandman-Goddard, G., Shoenfeld, Y. (2009). Parasitic infection and autoimmunity. Lupus 18: 1144-1148 [Abstract]  


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