Research Article The Acute Phase of Trypanosoma cruzi Infection Is Attenuated in 5-Lipoxygenase-Deficient Mice Adriana M. C. Canavaci, 1 Carlos A. Sorgi, 1 Vicente P. Martins, 2 Fabiana R. Morais, 1 Érika V. G. de Sousa, 1 Bruno C. Trindade, 1 Fernando Q. Cunha, 3 Marcos A. Rossi, 4 David M. Aronoff, 5 Lúcia H. Faccioli, 1 and Auro Nomizo 1 1 Departamento de An´ alises Cl´ ınicas, Toxicol´ ogicas e Bromatol´ ogicas, Faculdade de Ciˆ encias Farmacˆ euticas de Ribeir˜ ao Preto, Universidade de S˜ ao Paulo, Avenida do Caf´ e, s/n, 14040-903 Ribeir˜ ao Preto, SP, Brazil 2 Departamento de Biologia Celular, Instituto de Ciˆ encias Biol´ ogicas, Universidade de Bras´ ılia, Campus Darcy Ribeiro, 70910-900 Bras´ ılia, DF, Brazil 3 Departamento de Farmacologia, Faculdade de Medicina de Ribeir˜ ao Preto, Universidade de S˜ ao Paulo, Avenida Bandeirantes, No. 3900, 14049-900 Ribeir˜ ao Preto, SP, Brazil 4 Departamento de Patologia, Faculdade de Medicina de Ribeir˜ ao Preto, Universidade de S˜ ao Paulo, Avenida Bandeirantes, No. 3900, 14049-900 Ribeir˜ ao Preto, SP, Brazil 5 Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA Correspondence should be addressed to Auro Nomizo; aunomizo@fcfrp.usp.br Received 4 April 2014; Revised 12 June 2014; Accepted 17 June 2014; Published 3 August 2014 Academic Editor: Marcelo T. Bozza Copyright © 2014 Adriana M. C. Canavaci et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In the present work we examine the contribution of 5-lipoxygenase- (5-LO-) derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO −/− ) mice and wild-type (WT) mice. Compared with WT mice, the 5-LO −/− mice developed less parasitemia/tissue parasitism, less inlammatory cell iniltrates, and a lower mortality. his resistance of 5-LO −/− mice correlated with several diferences in the immune response to infection, including reduced PGE 2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL)-12 early in the infection; enhanced splenocyte production of IL-1, IL-6, and IFN-; rapid T-cell polarization to secrete high quantities of IFN- and low quantities of IL-10; and greater numbers of CD8 + CD44 high CD62L low memory efector T cells at the end of the acute phase of infection. he high mortality in WT mice was associated with increased production of LTB 4 /LTC 4 , T cell bias to produce IFN-, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. hese data also provide evidence that 5-LO-derived mediators negatively afect host survival during the acute phase of T. cruzi infection. 1. Introduction Infection with Trypanosoma cruzi (T. cruzi), an obligate intra- cellular protozoan parasite, causes American trypanosomia- sis or Chagas disease, a zoonosis endemic to Latin America. Approximately 60 million people live in areas with vector- borne transmission risk and the disease causes an estimated 14,000 deaths per year [1]. Ater entering the host, T. cruzi invades a variety of cell types, such as macrophages, heart muscle cells, skeletal muscle cells, and neurons, replicating within the cytoplasm [2]. he acute phase of the disease is characterized by a marked increase in parasite replication and migration to the blood, potentially leading to systemic infection. However, immunocompetent hosts are able to generate innate inlammatory and speciic immune responses to acute secondary infection, thereby controlling the parasite burden [3]. hese responses are primarily dependent on cytokine/chemokine mediated activation of infected phago- cytes and/or tissue cells which leads to intracellular killing [4], although complete elimination of the parasite is rarely Hindawi Publishing Corporation Mediators of Inflammation Volume 2014, Article ID 893634, 17 pages http://dx.doi.org/10.1155/2014/893634