Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Research Article J Innate Immun 2011;3:71–82 DOI: 10.1159/000320641 Rat Models to Investigate Host Macrophage Defense against Trypanosoma cruzi Daniela L. Fabrino   a, b Leonor Laura Leon   b Marcelo Genestra   b, 1 Gleydes G. Parreira   c Rossana C.N. Melo   a   a  Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, UFJF, Juiz de Fora, b  Laboratory of Biochemistry of Trypanosomatids, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, and c  Department of Morphology, Federal University of Minas Gerais, UFMG, Belo Horizonte, Brazil ited by an arginase-dependent mechanism. Our work dem- onstrates differential responses of Holtzman and Wistar rats to T. cruzi, and highlights the use of Holtzman rats as useful models for further studies of cardiac/skeletal muscle tropism and innate immune responses that protect the host against parasite replication. This is important for the development of proper therapeutic interventions. Copyright © 2010 S. Karger AG, Basel Parasitic protozoa infect hundreds of millions of peo- ple every year and are collectively some of the most im- portant causes of human misery [1]. The flagellated pro- tozoa Trypanosoma cruzi is the causal agent of Chagas’ disease (also known as American trypanosomiasis) dis- covered around a century ago by the Brazilian physician Carlos Chagas [2]. This disease remains a major problem with a great impact on public health in Latin America. Unfortunately, there is no vaccine available to prevent Chagas’ disease. While different tools to manage the infection with re- gard to detection and treatment have been discussed [3], biological research is still critical to understand basic as- Key Words Chagas’ disease  Trypanosoma cruzi  Inflammation  Monocytes/macrophages  Innate immunity  Heart  Parasitism  Immunopathology  Rats Abstract Trypanosoma cruzi is the causal agent of Chagas’ disease, an infection with a great impact on public health in Latin Amer- ica. One of the challenges to understand Chagas’ disease lies on the complex host-parasite interaction. The understand- ing of this interaction requires the use of appropriate exper- imental models that mimic the human disease. Here, we have used two lineages of rats (Wistar and Holtzman) to comparatively evaluate the course of the acute infection (Y strain). Infection was monitored by parasitemia, cardiac and skeletal muscle parasitism and inflammation, heart ultra- structure, recruitment of monocytes/macrophages and ni- tric oxide, and arginase production by these cells. Although both rats were able to infect, only Holtzman rats developed a marked infection in the cardiac and skeletal muscles, in parallel to a high recruitment of first-line defense cells. A high number of inflammatory macrophages directed para- site clearance. By the end of the acute phase, Holtzman rats showed consistent disease control. Interestingly, parasite killing was not related to nitric oxide production likely inhib- Received: December 7, 2009 Accepted after revision: August 24, 2010 Published online: November 3, 2010 Journal of Innate Immunity Dr. Rossana C.N. Melo Laboratory of Cellular Biology, Department of Biology Federal University of Juiz de Fora, UFJF Juiz de Fora, MG 36036-900 (Brazil) Tel. +55 32 3229 3206, ext. 215, Fax +55 32 3229 3227, E-Mail rossana.melo  @  ufjf.edu.br © 2010 S. Karger AG, Basel 1662–811X/11/0031–0071$38.00/0 Accessible online at: www.karger.com/jin 1 In memoriam.