Multicellular intestinal nematode parasites can cross the epithelial barrier potentially causing tissue damage and release of danger associated molecular patterns (DAMPs) that may promote type 2 responses and host protective immunity. We investigated whether adenosine specifically binding the A2B adenosine receptor (A2BAR) on epithelial cells played an important role in driving intestinal immunity. Specific blockade of epithelial cell A2BAR inhibited the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri, including disruption of granuloma development at the host:parasite interface during the transient tissue dwelling larval stage. Memory T cell development was blocked during the primary response and transcriptional analyses revealed profound impairment of A2BAR signaling in epithelial cells and reduced type 2 markers by 24 hours after inoculation. Extracellular ATP was visualized by 24 hours after inoculation and shown in CD39 deficient mice to be critical for the adenosine production mediating initiation of type 2 immunity.

中文翻译：

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通过细胞外ATP代谢的腺苷通过触发肠上皮细胞上的A2BAR信号传导来促进2型免疫

多细胞肠道线虫寄生虫可以越过上皮屏障，从而潜在地导致组织损伤并释放可能促进2型反应和宿主保护性免疫的危险分子模式（DAMP）。我们调查了腺苷是否特异性结合上皮细胞上的A2B腺苷受体（A2BAR）在驱动肠道免疫中起重要作用。上皮细胞A2BAR的特异性阻滞抑制了宿主对肠蠕虫Heligmosomoides polygyrus bakeri的保护性记忆反应，包括破坏了在瞬时组织驻留幼虫阶段宿主：寄生虫界面上的肉芽肿发展。记忆T细胞的发育在主要反应期间受到阻滞，转录分析显示上皮细胞中A2BAR信号传导严重受损，接种后24小时内2型标记物减少。接种后24小时即可看到细胞外ATP，并在CD39缺陷型小鼠中显示出对于介导2型免疫起始的腺苷产生至关重要。