IL-17A-Producing γδ T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver
IL-17A-Producing γδ T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver
复制标题
DOI：
10.4049/jimmunol.1501046
复制
发表时间：
2015-12-15
影响因子：
4.4
通讯作者：
Engwerda, Christian R.
中科院分区：
文献类型：
--
作者：
Sheel, Meru;Beattie, Lynette;Engwerda, Christian R.
细胞内感染，如由原生动物寄生虫杜氏利什曼原虫（内脏利什曼病（VL）的病原体）引起的感染，需要有效的宿主促炎反应来控制。IL-17已成为限制细胞外和细胞内病原体生长所需的重要促炎细胞因子。然而，关于IL-17在寄生虫感染期间的确切作用存在相互矛盾的报道，并且关于细胞来源及其调节的免疫途径的知识有限。我们研究了IL-17在由L. donovani的研究，并确定了IL-17在肝脏中的早期抑制作用，限制了对寄生虫生长的控制。在感染的第一周募集到肝脏的产生IL-17的γ δ T细胞是该模型中IL-17的关键来源，并且CCR 2（+）炎性单核细胞是IL-17抑制作用的重要靶点。改进的寄生虫控制是独立的NO生成，但与维护超氧化物歧化酶mRNA的表达在肝脏中的IL-17的情况下。因此，我们已经确定了一种新的抑制功能IL-17寄生虫感染，我们的研究结果表明，重要的相互作用之间的gd T细胞，单核细胞和感染的巨噬细胞在肝脏中，可以确定寄生虫感染的结果。
Intracellular infections, such as those caused by the protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis (VL), require a potent host proinflammatory response for control. IL-17 has emerged as an important proinflammatory cytokine required for limiting growth of both extracellular and intracellular pathogens. However, there are conflicting reports on the exact roles for IL-17 during parasitic infections and limited knowledge about cellular sources and the immune pathways it modulates. We examined the role of IL-17 in an experimental model of VL caused by infection of C57BL/6 mice with L. donovani and identified an early suppressive role for IL-17 in the liver that limited control of parasite growth. IL-17-producing gamma delta T cells recruited to the liver in the first week of infection were the critical source of IL-17 in this model, and CCR2(+) inflammatory monocytes were an important target for the suppressive effects of IL-17. Improved parasite control was independent of NO generation, but associated with maintenance of superoxide dismutase mRNA expression in the absence of IL-17 in the liver. Thus, we have identified a novel inhibitory function for IL-17 in parasitic infection, and our results demonstrate important interactions among gd T cells, monocytes, and infected macrophages in the liver that can determine the outcome of parasitic infection.