The increase in mannose receptor recycling favors arginase induction and Trypanosoma cruzi survival in macrophages.
The increase in mannose receptor recycling favors arginase induction and Trypanosoma cruzi survival in macrophages.
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DOI：
10.7150/ijbs.7.1257
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发表时间：
2011
影响因子：
9.2
通讯作者：
Cerbán FM
中科院分区：
文献类型：
--
作者：
Garrido VV;Dulgerian LR;Stempin CC;Cerbán FM
巨噬细胞甘露糖受体（MR）是先天免疫系统的模式识别受体，其结合到在其表面上带有甘露糖、岩藻糖和N-乙酰葡糖胺的微生物结构。克氏锥虫抗原cruzipain（Cz）存在于寄生虫的不同发育形式中。该糖蛋白具有参与宿主-抗原接触的高度甘露糖基化的C-末端结构域。我们的小组先前证明，Cz-巨噬细胞（Mo）相互作用可以调节针对T. cruzi通过诱导优先代谢途径。在这项工作中，我们已经研究了在钼的作用，MR的诱导和T。使用不同MR配体的cruzi生存率。我们已经证明T.用甘露糖-牛血清白蛋白（Man-BSA，MR特异性配体）感染的细胞使一氧化氮（NO）/尿素平衡偏向尿素产生，并增加细胞内无鞭毛体的生长。胞内信号的研究表明，Man-BSA预孵育T。cruzi J774感染细胞后JNK和p44/p42磷酸化水平下调，p38 MAPK磷酸化水平升高。这些结果与先前的数据一致，表明Cz也改变了寄生虫诱导的MAPK磷酸化谱。此外，我们已经通过共聚焦显微镜表明，Cz和Man-BSA增强MR再循环。此外，我们还研究了T.体内克氏感染。T.在感染后13和15天，Cruzi感染小鼠。此外，我们还研究了MR封闭抗体对T。克氏杆菌感染的腹膜Mo.与用对照抗体处理的感染细胞相比，用抗MR抗体预孵育的感染细胞中的精氨酸酶活性和寄生虫生长减少。因此，我们假设，在T。克鲁兹感染后，Cz可能与MR接触，增加MR回收，导致精氨酸酶活性上调和细胞内寄生虫生长。
The macrophage mannose receptor (MR) is a pattern recognition receptor of the innate immune system that binds to microbial structures bearing mannose, fucose and N-acetylglucosamine on their surface. Trypanosoma cruzi antigen cruzipain (Cz) is found in the different developmental forms of the parasite. This glycoprotein has a highly mannosylated C-terminal domain that participates in the host-antigen contact. Our group previously demonstrated that Cz-macrophage (Mo) interaction could modulate the immune response against T. cruzi through the induction of a preferential metabolic pathway. In this work, we have studied in Mo the role of MR in arginase induction and in T. cruzi survival using different MR ligands. We have showed that pre-incubation of T. cruzi infected cells with mannose-Bovine Serum Albumin (Man-BSA, MR specific ligand) biased nitric oxide (NO)/urea balance towards urea production and increased intracellular amastigotes growth. The study of intracellular signals showed that pre-incubation with Man-BSA in T. cruzi J774 infected cells induced down-regulation of JNK and p44/p42 phosphorylation and increased of p38 MAPK phosphorylation. These results are coincident with previous data showing that Cz also modifies the MAPK phosphorylation profile induced by the parasite. In addition, we have showed by confocal microscopy that Cz and Man-BSA enhance MR recycling. Furthermore, we studied MR behavior during T. cruzi infection in vivo. MR was up-regulated in F4/80+ cells from T. cruzi infected mice at 13 and 15 days post infection. Besides, we investigated the effect of MR blocking antibody in T. cruzi infected peritoneal Mo. Arginase activity and parasite growth were decreased in infected cells pre-incubated with anti-MR antibody as compared with infected cells treated with control antibody. Therefore, we postulate that during T. cruzi infection, Cz may contact with MR, increasing MR recycling which leads to arginase activity up-regulation and intracellular parasite growth.
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