Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile toxin (LT) modulates the expression of many genes in intestinal epithelia, including carcinoembryonic cell adhesion molecules (CEACAMs) which ETEC exploit as receptors, enabling toxin delivery. Here, however, we demonstrate that LT also enhances the expression of CEACAMs on extracellular vesicles (EV) shed by intestinal epithelia and that CEACAM-laden EV increase in abundance during human infections, mitigate pathogen–host interactions, scavenge free ETEC toxins, and accelerate ETEC clearance from the gastrointestinal tract. Collectively, these findings indicate that CEACAMs play a multifaceted role in ETEC pathogen–host interactions, transiently favoring the pathogen, but ultimately contributing to innate responses that extinguish these common infections.

中文翻译：

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宿主来源的载有 CEACAM 的囊泡与产肠毒素的大肠杆菌结合以消除和中和毒素


产肠毒素大肠埃希菌 （ETEC） 每年导致数亿例腹泻疾病，从轻微症状的病例到严重的、危及生命的霍乱样腹泻。尽管 ETEC 与包括营养不良在内的长期后遗症有关，但急性腹泻病在很大程度上是自限性的。最近的研究表明，除了引起腹泻外，ETEC 热不稳定毒素 （LT） 还调节肠上皮细胞中许多基因的表达，包括癌胚细胞粘附分子 （CEACAM），ETEC 将其用作受体，使毒素递送成为可能。然而，在这里，我们证明 LT 还增强了肠上皮细胞脱落的细胞外囊泡 （EV） 上 CEACAM 的表达，并且载有 CEACAM 的 EV 在人类感染期间丰度增加，减轻病原体-宿主相互作用，清除游离的 ETEC 毒素，并加速胃肠道的 ETEC 清除。总的来说，这些发现表明 CEACAM 在 ETEC 病原体-宿主相互作用中发挥着多方面的作用，暂时有利于病原体，但最终有助于消除这些常见感染的先天反应。