蠕虫感染导致寄生虫在人类和动物中过度分散。我们询问了针对迁移的A虫幼虫的早期免疫反应是否会导致蠕虫在自然宿主种群中的分布不均,因此研究了易感和抗性小鼠品系。在老鼠身上,蛔虫幼虫发育到肺阶段,因此可以破译针对肝脏和肺中迁移幼虫的早期抗A虫免疫反应。我们的数据显示,与抗性CBA小鼠相比,易感C57BL/6小鼠对A虫幼虫迁移的反应明显更强,并且抗寄生虫反应性与病理学相关。在肝脏和肺部检测到嗜酸性粒细胞募集增加,而且在感染后第8天易感小鼠的脾脏和腹膜腔中,与耐药小鼠相比。在血清中,嗜酸性粒细胞过氧化物酶水平仅在易感小鼠中显著较高,表明招募的嗜酸性粒细胞的功能活动。这种作用与先天淋巴细胞和CD4T细胞产生的IL-5/IL-13的增加以及易感小鼠肺中明显的2型巨噬细胞极化有关。此外,野生型BALB/c和嗜酸性粒细胞缺陷型dblGATA-1BALB/c小鼠的比较表明,嗜酸性粒细胞对于早期控制迁移的蛔虫幼虫不是必需的.总之,在原发性感染中,肝气管蠕虫幼虫迁移过程中强烈的局部和全身2型免疫反应与病理而不是保护有关。
Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In
mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6
mice respond to Ascaris larval migration significantly stronger compared to resistant CBA
mice and the anti-parasite reactivity is associated with pathology. Increased eosinophil recruitment was detected in the liver and lungs, but also in the spleen and peritoneal cavity of susceptible mice on day 8 post infection compared to resistant
mice. In serum, eosinophil peroxidase levels were significantly higher only in the susceptible mice, indicating functional activity of the recruited eosinophils. This effect was associated with an increased IL-5/IL-13 production by innate lymphoid cells and CD4+ T cells and a pronounced type 2 macrophage polarization in the lungs of susceptible mice. Furthermore, a comparison of wildtype BALB/c and eosinophil-deficient dblGATA-1 BALB/c
mice showed that eosinophils were not essential for the early control of migrating Ascaris larvae. In conclusion, in primary infection, a strong local and systemic type 2 immune response during hepato-tracheal helminth larval migration is associated with pathology rather than protection.