Demiri M, Müller-Luda K, Agace W W, Svensson-Frej M
Immunology Section, Lund University, Lund, Sweden.
Section of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Lyngby, Denmark.
Parasite Immunol. 2017 Oct;39(10). doi: 10.1111/pim.12458. Epub 2017 Sep 5.
Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC.
用鼠类大肠线虫毛首鞭形线虫进行低剂量和高剂量感染，分别与肠系膜淋巴结（MLN）中适应性Th1和Th2反应的诱导有关。在毛首鞭形线虫感染后，经典树突状细胞（cDC）会在大肠黏膜和MLN中积聚，但其在驱动对感染的适应性反应中的作用仍 largely 未知。我们对缺乏特定cDC亚群的小鼠进行了低剂量和高剂量的毛首鞭形线虫感染，以研究它们在诱导适应性免疫反应中的作用。缺乏IRF4依赖性cDC的小鼠无法清除高剂量感染，且Th2反应受损。相反，缺乏IRF8依赖性cDC的小鼠清除了低剂量感染，Th1反应受损，同时Th2细胞因子的产生增加。最后，缺乏IRF4和IRF8依赖性cDC的小鼠能够产生Th2反应并清除低剂量感染。总体而言，这些结果表明，IRF4和IRF8依赖性cDC在毛首鞭形线虫感染期间起拮抗作用，并证明在没有IRF4依赖性cDC的情况下，肠道可针对毛首鞭形线虫产生Th2反应。
