Bradford Barry M, Donaldson David S, Forman Ruth, Else Kathryn J, Mabbott Neil A
The Roslin Institute & Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Parasite Immunol. 2018 Aug;40(8):e12566. doi: 10.1111/pim.12566.
Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum and proximal colon. The rapid expulsion of T. muris in resistant mouse strains is associated with the induction of a protective T helper cell type 2 (Th2)-polarized immune response. Susceptible mouse strains, in contrast, mount an inappropriate Th1 response to T. muris infection. Expression of the chemokine CXCL13 by stromal follicular dendritic cells attracts CXCR5-expressing cells towards the B-cell follicles. Previous studies using a complex in vivo depletion model have suggested that CXCR5-expressing conventional dendritic cells (cDC) help regulate the induction of Th2-polarized responses. Here, transgenic mice with CXCR5 deficiency specifically restricted to CD11c cells were used to determine whether the specific absence CXCR5 on CD11c cells such as cDC would influence susceptibility to oral T. muris infection by affecting the Th1/Th2 balance. We show that in contrast to control mice, those which lacked CXCR5 expression on CD11c cells failed to clear T. muris infection and developed cytokine and antibody responses that suggested a disturbed Th1/Th2 balance with enhanced IFN-γ expression. These data suggest an important role of CXCR5-expressing CD11c cells such as cDC in immunity to oral T. muris infection.
毛首鞭形线虫是一种天然的小鼠肠道蠕虫病原体，它特异性地在盲肠和近端结肠建立感染。在抗性小鼠品系中，毛首鞭形线虫的快速排出与诱导保护性2型辅助性T细胞（Th2）极化免疫反应有关。相比之下，易感小鼠品系对毛首鞭形线虫感染产生不适当的Th1反应。基质滤泡树突状细胞表达的趋化因子CXCL13将表达CXCR5的细胞吸引到B细胞滤泡。先前使用复杂的体内耗竭模型的研究表明，表达CXCR5的常规树突状细胞（cDC）有助于调节Th2极化反应的诱导。在这里，使用CXCR5缺陷特异性局限于CD11c细胞的转基因小鼠来确定CD11c细胞（如cDC）上CXCR5的特异性缺失是否会通过影响Th1/Th2平衡来影响口服毛首鞭形线虫感染的易感性。我们发现，与对照小鼠相比，CD11c细胞上缺乏CXCR5表达的小鼠未能清除毛首鞭形线虫感染，并产生了细胞因子和抗体反应，这表明Th1/Th2平衡受到干扰，IFN-γ表达增强。这些数据表明，表达CXCR5的CD11c细胞（如cDC）在口服毛首鞭形线虫感染的免疫中起重要作用。
