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Depletion of regulatory T cells decreases cardiac parasitosis and inflammation in experimental Chagas disease

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Abstract

Infection with the protozoan parasite Trypanosoma cruzi may lead to a potentially fatal cardiomyopathy known as Chagas heart disease. This disease is characterized by infiltration of the myocardium by mononuclear cells, including CD4+ T cells, together with edema, myofibrillary destruction, and fibrosis. A multifaceted systemic immune response develops that ultimately keeps parasitemia and tissue parasitosis low. T helper 1 and other pro-inflammatory T cell responses are effective at keeping levels of T. cruzi low in tissues and blood, but they may also lead to tissue inflammation when present chronically. The mechanism by which the inflammatory response is regulated in T. cruzi-infected individuals is complex, and the specific roles that Th17 and T regulatory (Treg) cells may play in that regulation are beginning to be elucidated. In this study, we found that depletion of Treg cells in T. cruzi-infected mice leads to reduced cardiac parasitosis and inflammation, accompanied by an augmented Th1 response early in the course of infection. This is followed by a downregulation of the Th1 response and increased Th17 response late in infection. The effect of Treg cell depletion on the Th1 and Th17 cells is not observed in mice immunized with T. cruzi in adjuvant. This suggests that Treg cells specifically regulate Th1 and Th17 cell responses during T. cruzi infection and may also be important for modulating parasite clearance and inflammation in the myocardium of T. cruzi-infected individuals.

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Acknowledgments

We thank Teresa Schuessler for helpful advice during this study. This work was supported by NIH grants HL075822 and HL80692 (to D.M.E.) and Predoctoral Fellowship 0810179Z from the American Heart Association (to K.M.B.).

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Authors and Affiliations

  1. Liberal Studies, Faculty of Arts and Sciences, New York University, New York, NY, USA

    Kevin M. Bonney

  2. Departments of Pathology, Pediatrics and Microbiology-Immunology, and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL, USA

    Joann M. Taylor, Edward B. Thorp, Conrad L. Epting & David M. Engman

  3. Department of Pathology, Northwestern University, Ward Building 4-116 303 E. Chicago Ave., Chicago, IL, 60611, USA

    David M. Engman

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  1. Kevin M. Bonney
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Bonney, K.M., Taylor, J.M., Thorp, E.B. et al. Depletion of regulatory T cells decreases cardiac parasitosis and inflammation in experimental Chagas disease. Parasitol Res 114, 1167–1178 (2015). https://doi.org/10.1007/s00436-014-4300-3

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