Th2 memory responses to an intestinal helminth infection

Th2记忆对肠道蠕虫感染的反应

• 批准号: 396638922
• 负责人: Professorin Dr. Susanne Hartmann
• 金额: --
• 依托单位: Institut für Immunologie (WE06)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/396638922?language=en
• 关键词: Th2; memory; responses; intestinal; helminth

The current funding period revealed three main aspects of Th2 memory against intestinal nematodes: (i) the peritoneum plays a key role in the maintenance of memory Th2 cells after abrogation of primary infection; (ii) immunization with helminth excretory/secretory (E/S) products induces a level of protection similar to that of natural infection against reinfection, which specifically depends on long-lived functional memory T cells; (iii) Th2 memory cell formation, tissue distribution, and recall response are independent of host microbiota. Based on these findings, we aim to expand the knowledge of the mechanisms of Th2 memory cell recruitment and reactivation against intestinal helminths in the prolongation phase. The following hypotheses will be investigated: A) The peritoneum is essential for the recirculation of effector and memory Th2 cells for a protective immune response against intestinal nematodes. This will be investigated by a) adoptive transfers to determine whether peritoneal memory Th2 cells migrate to the small intestine upon re-infection with nematodes and b) blocking cellular adhesion markers to decipher whether their interaction is essential for recruitment, retention and relocalization of peritoneal Th2 cells. B) Cytokine environment and local antigen presentation in the peritoneal cavity are essential for Th2 memory cell reactivation. Here, we plan to focus on the role of IL-27 as a regulator of Th2 memory cell formation and reactivation in the peritoneum and to investigate whether the reactivation of Th2 memory cells in the peritoneum after infection is an antigen-dependent process. C) Mesenteric fat is an important reservoir of Th2 memory cells in intestinal nematode infections and promotes protective immune responses against parasite E/S products. Based on preliminary data showing that mesenteric fat contains Th2 memory cells more than a year after primary nematode infection, we aim to decipher whether Th2 cells interact with adipocytes during primary infection, memory stage, and reinfection with gastrointestinal nematodes and after immunization with E/S products of intestinal nematodes.

目前的资助期揭示了针对肠道线虫的Th 2记忆的三个主要方面：（i）腹膜在消除初次感染后维持记忆Th 2细胞中起关键作用;（ii）用蠕虫排泄/分泌（E/S）产物免疫诱导类似于自然感染的针对再感染的保护水平，这特别依赖于长寿命的功能性记忆T细胞;（iii）Th 2记忆细胞的形成、组织分布和回忆反应与宿主微生物群无关。基于这些发现，我们的目标是扩大知识的机制，Th 2记忆细胞的招聘和重新激活对肠道蠕虫在延长阶段。将研究以下假设：A）腹膜对于效应和记忆Th 2细胞的再循环对于针对肠线虫的保护性免疫应答是必不可少的。这将通过以下方法进行研究：a）过继转移，以确定腹膜记忆性Th 2细胞在线虫再感染后是否迁移到小肠，和B）阻断细胞粘附标记物，以解释它们的相互作用是否对腹膜Th 2细胞的募集、保留和重新定位是必需的。B）腹膜腔中的细胞因子环境和局部抗原呈递对于Th 2记忆细胞再活化是必需的。在这里，我们计划集中在IL-27的作用，作为一个调节器的Th 2记忆细胞的形成和再激活的腹膜，并调查感染后的Th 2记忆细胞在腹膜的再激活是否是一个抗原依赖性的过程。C）肠系膜脂肪是肠道线虫感染中Th 2记忆细胞的重要储库，并促进针对寄生虫E/S产物的保护性免疫应答。初步数据显示，肠系膜脂肪中含有Th 2记忆细胞一年多后，主要线虫感染，我们的目标是破译是否Th 2细胞与脂肪细胞在初次感染，记忆阶段，再感染与胃肠道线虫和免疫后的E/S产品的肠道线虫。