Data_Sheet_1_Nematode-Infected Mice Acquire Resistance to Subsequent Infection With Unrelated Nematode by Inducing Highly Responsive Group 2 Innate Lymphoid Cells in the Lung.PDF

The immune responses against helminths have been investigated individually, and it is well-established that infected hosts develop an immunological memory to resist reinfection by the same pathogen. In contrast, it is poorly understood how the host immune system responds to subsequent infection by unrelated parasites after elimination of the first infection. We previously reported that infection of mice with Strongyloides venezuelensis induces the accumulation of group 2 innate lymphoid cells (ILC2s) in the lung. Here, we demonstrated that S. venezuelensis-experienced (Sv-exp) mice became significantly resistant against infection by Nippostrongylus brasiliensis. N. brasiliensis infection induced enhanced accumulation of ILC2s and eosinophils with increased expressions of mRNA for Th2 cytokines in the lungs of Sv-exp mice. The resistance was dependent on ILC2s, and eosinophils but not on CD4+ T cells. Furthermore, pulmonary ILC2s in Sv-exp mice acquired a highly responsive “trained” phenotype; in response to N. brasiliensis infection, they rapidly increased and produced IL-5 and IL-13, which in turn induced the early accumulation of eosinophils in the lungs. IL-33 was required for the accumulation of ILC2s and the resistance of mice against N. brasiliensis infection but insufficient for the induction of trained ILC2s. In conclusion, animals infected with one type of lung-migratory nematodes acquire a specific-antigen-independent resistance to another type of lung-migrating nematodes, providing animals with the capacity to protect against sequential infections with various lung-migratory nematodes.

针对蠕虫的免疫应答既往多为单独研究，目前已有明确定论：受感染宿主会形成免疫记忆，以抵御同一病原体的再次感染。与之形成鲜明对比的是，宿主免疫系统在清除首次感染后，如何应对后续无关寄生虫感染的相关机制仍知之甚少。我们此前曾报道，委内瑞拉类圆线虫（Strongyloides venezuelensis）感染小鼠可诱导肺部2型天然淋巴细胞（group 2 innate lymphoid cells, ILC2s）聚集。本研究证实，经委内瑞拉类圆线虫致敏（Sv-exp）小鼠对巴西日圆线虫（Nippostrongylus brasiliensis）感染的抵抗力显著增强。巴西日圆线虫感染可使经致敏小鼠肺部的ILC2s与嗜酸性粒细胞的聚集增强，且Th2细胞因子的mRNA表达水平升高。该抵抗力依赖于ILC2s与嗜酸性粒细胞，而非CD4+ T细胞。进一步研究发现，经委内瑞拉类圆线虫致敏小鼠的肺部ILC2s获得了高度应答的“训练型”表型：在遭遇巴西日圆线虫感染时，这些ILC2s会快速增殖并分泌IL-5与IL-13，进而诱导嗜酸性粒细胞在肺部早期聚集。IL-33对于ILC2s的聚集以及小鼠抵御巴西日圆线虫感染是必需的，但不足以诱导训练型ILC2s的形成。综上，感染过一类肺迁徙线虫的动物，可获得针对另一类肺迁徙线虫的抗原非特异性抵抗力，使动物能够抵御多种肺迁徙线虫的先后感染。