The Journal of experimental medicine · 2022
Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Karo-Atar Danielle, Ouladan Shaida, Javkar Tanvi, Joumier Loick, Matheson Macy K, Merritt Sydney, Westfall Susan, Rochette Annie, Gentile Maria E, Fontes Ghislaine, Fonseca Gregory J, Parisien Marc, Diatchenko Luda, von Moltke Jakob, Malleshaiah Mohan, Gregorieff Alex, King Irah L
Аннотация
Enteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the parasite Heligmosomoides polygyrus bakeri (Hpb) reprograms the intestinal epithelium into a fetal-like state marked by the emergence of Clusterin-expressing revival stem cells (revSCs). Organoid-based studies using parasite-derived excretory-secretory products reveal that Hpb-mediated revSC generation occurs independently of host-derived immune signals and inhibits type 2 cytokine-driven differentiation of secretory epithelial lineages that promote their expulsion. Reciprocally, type 2 cytokine signals limit revSC differentiation and, consequently, Hpb fitness, indicating that helminths compete with their host for control of the intestinal stem cell compartment to promote continuation of their life cycle.