The Receptor Slamf 1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite responsible for Chagas’ disease, causes severe myocarditis often resulting in death. Here, we report that Slamf12/2 mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf12/2 mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-c production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-c in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection. Citation: Calderón J, Maganto-Garcia E, Punzón C, Carrión J, Terhorst C, et al. (2012) The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi. PLoS Pathog 8(7): e1002799. doi:10.1371/journal.ppat.1002799 Editor: David L. Sacks, National Institute of Health, United States of America Received February 4, 2012; Accepted May 30, 2012; Published July 12, 2012 Copyright: 2012 Calderón et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported in part by grants FIS (PI040993), Ministerio de Ciencia e Innovación (SAF2005-02220, SAF2007-61716 and SAF2010-18733), European Union (Eicosanox and ChagasEpiNet), CSIC-CONICET, BSCH/UAM, Comunidad de Madrid S2010/BMD-2332, RED RECAVA RD06/0014/1013 and RED RICET RD06/0021/0016 to MF, a grant from the NIH to CT (AI-15066), and an institutional grant of Fundacion Ramon Areces. J.C. is a holder of a fellowship from the Government of Panama. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: mfresno@cbm.uam.es ¤a Current address: Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ¤b Current address: Facultad de Veterinaria, Universidad Complutense de Madrid, Spain