1. Host-derived CEACAM-laden vesicles engage enterotoxigenic Escherichia coli for elimination and toxin neutralization.
- Author
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Sheikh A, Ganguli D, Vickers TJ, Singer BB, Foulke-Abel J, Akhtar M, Khatoon N, Setu B, Basu S, Harro C, Maier N, Beatty WL, Chakraborty S, Bhuiyan TR, Qadri F, Donowitz M, and Fleckenstein JM
- Subjects
- Humans, Extracellular Vesicles metabolism, Intestinal Mucosa metabolism, Intestinal Mucosa microbiology, Animals, Mice, Antigens, CD metabolism, Antigens, CD genetics, Carcinoembryonic Antigen metabolism, Carcinoembryonic Antigen genetics, Cell Adhesion Molecules metabolism, Cell Adhesion Molecules genetics, Diarrhea microbiology, Diarrhea metabolism, Enterotoxigenic Escherichia coli metabolism, Escherichia coli Infections microbiology, Escherichia coli Infections immunology, Escherichia coli Infections metabolism, Escherichia coli Proteins metabolism, Escherichia coli Proteins genetics, Host-Pathogen Interactions, Enterotoxins metabolism, Bacterial Toxins metabolism
- Abstract
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., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2024
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