The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

PLoS Pathogens

Javier Carrión¹  Manuel Fresno¹  Jossela Calderón¹  Carmen Punzón¹  Elena Maganto-Garcia²  Cox Terhorst² 

[1] Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain;Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain

关键词: Trypanosoma cruzi;    Parasitic diseases;    Heart;    Macrophages;    Amastigotes;    Cytokines;    Protozoan infections;    Bone marrow cells;   

DOI  :  10.1371/journal.ppat.1002799

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1−/− mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1−/− 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-γ 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-γ 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.

【 授权许可】

CC BY