在初次感染中,针对身体迁移的蛔虫幼虫的 Th2 偏向性免疫反应与病理学相关,但与保护无关。

Th2-biased immune responses to body migrating Ascaris larvae in primary infection are associated with pathology but not protection.

机构信息

Institute of Immunology, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, iPATH.Berlin, Berlin, Germany.

出版信息

Sci Rep. 2024 Jun 28;14(1):14919. doi: 10.1038/s41598-024-65281-0.

Abstract

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.

摘要

寄生虫感染会导致人类和动物体内寄生虫的离散度增加。我们想知道针对迁移性蛔虫幼虫的早期免疫反应是否是导致自然宿主种群中蠕虫分布不均的原因,因此我们研究了易感和抗性两种小鼠品系。在小鼠中,蛔虫幼虫发育到肺部阶段,因此可以研究肝脏和肺部中针对迁移性幼虫的早期抗蛔虫免疫反应。我们的数据表明,与抗性 CBA 小鼠相比,易感 C57BL/6 小鼠对蛔虫幼虫迁移的反应要强得多,并且这种抗寄生虫反应与病理学有关。与抗性小鼠相比,感染后第 8 天,易感小鼠的肝脏和肺部以及脾脏和腹腔中检测到嗜酸性粒细胞募集增加。在血清中,只有易感小鼠的嗜酸性粒细胞过氧化物酶水平显著升高,表明募集的嗜酸性粒细胞具有功能活性。这种效应与固有淋巴细胞和 CD4 T 细胞中 IL-5/IL-13 产生的增加以及易感小鼠肺部 2 型巨噬细胞的显著极化有关。此外,野生型 BALB/c 和嗜酸性粒细胞缺陷型 dblGATA-1 BALB/c 小鼠的比较表明,嗜酸性粒细胞对于迁移性蛔虫幼虫的早期控制并非必需。总之,在初次感染中,在肝肺寄生虫幼虫迁移期间发生强烈的局部和全身性 2 型免疫反应与病理学有关,而与保护无关。

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