The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi
The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi
复制标题
DOI：
10.1371/journal.ppat.1002799
复制
发表时间：
2012-07-01
期刊：
影响因子：
6.7
通讯作者：
Fresno, Manuel
中科院分区：
文献类型：
--
作者：
Calderon, Jossela;Maganto-Garcia, Elena;Fresno, Manuel
克氏锥虫是引起恰加斯病的原生动物寄生虫，可引起严重的心肌炎，通常导致死亡。在这里，我们报告说，Slamf 1（-/-）小鼠，缺乏造血细胞表面受体Slamf 1，是完全保护免受急性致命的寄生虫的挑战。与感染相同剂量寄生虫的野生型小鼠相比，Slamf 1（-/-）小鼠的心脏损伤减少，这是由于心脏中寄生虫数量减少，即使寄生虫血症也只是轻微减少。体内和体外实验都表明，Slamf 1缺陷型骨髓细胞复制寄生虫的能力受损，并显示细胞因子的产生改变。重要的是，即使浸润树突状细胞、巨噬细胞、CD 4和CD 8 T淋巴细胞的数量相当，Slamf 1缺陷小鼠心脏中IFN-γ的产生也远低于野生型小鼠心脏中IFN-γ的产生。施用抗Slamf 1单克隆抗体也减少了心脏中寄生虫和IFN-γ的数量。这些观察结果不仅解释了寄生虫体内感染的易感性降低，而且它们还表明人Slamf 1作为针对T.克氏感染
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-gamma 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-gamma 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.