the receptor slamf1 on the surface of myeloid lineage cells controls susceptibility to infection by trypanosoma cruzi细胞表面受体slamf1淋系控制由鲁兹锥体对感染的易感性.pdfVIP

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi ´ 1,2 1¤a ´ 1,2 ´ 1¤b 3 Jossela Calderon , Elena Maganto-Garcia , Carmen Punzon , Javier Carrion , Cox Terhorst , Manuel Fresno1,2* ´ ´ ´ 1 Centro de Biologıa Molecular ‘‘Severo Ochoa’’ (CSIC-UAM), Universidad Autonoma de Madrid, Cantoblanco, Madrid, Spain, 2 Instituto de Investigacion Sanitaria Princesa (IP), Madrid, Spain, 3 The Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Trypanosoma cruzi, the protozoan parasite responsible for Chagas’ disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1 2/ 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