Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection
Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection
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DOI：
10.1038/mi.2016.56
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发表时间：
2017-03-01
影响因子：
8
通讯作者：
Breloer, M.
中科院分区：
文献类型：
--
作者：
Reitz, M.;Brunn, M-L;Breloer, M.
肥大细胞和嗜碱性粒细胞是先天免疫细胞，具有重叠的功能，有助于抗蠕虫免疫。先前使用肥大细胞缺陷的 Kit 突变小鼠研究了蠕虫感染期间的肥大细胞功能，这些小鼠表现出额外的与肥大细胞无关的免疫缺陷。在这里，我们以独立于试剂盒的方式使用缺乏嗜碱性粒细胞或粘膜和结缔组织肥大细胞的小鼠来重新评估每种细胞类型在蠕虫感染期间的影响。肥大细胞和嗜碱性粒细胞都不参与对组织迁移的鼠类圆线虫第三阶段幼虫的免疫反应，但这两种细胞类型都有助于早期将寄生成虫从肠道中排出。鼠链球菌感染的终止需要粘膜肥大细胞的存在：缺乏粘膜和结缔组织肥大细胞的Cpa3(Cre)小鼠，可保持感染超过150天。仅缺乏结缔组织肥大细胞的 Mcpt5(Cre) R-DTA 小鼠和嗜碱性粒细胞缺陷的 Mcpt8(Cre) 小鼠在 1 个月后以野生型动力学终止了感染，尽管它们最初肠道寄生虫负荷增加。由于 Cpa3(Cre) 小鼠表现出完整的 Th2 极化，并在疫苗接种后有效地产生了保护性免疫，因此我们假设粘膜肥大细胞是肠上皮中非冗余的终末效应细胞，它们执行抗蠕虫免疫，但不协调它。
Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit-independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3(Cre) mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5(Cre) R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8(Cre) mice terminated the infection after 1 month with wild-type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3(Cre) mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it.