Oral exposure to <i>Escherichia coli</i>toxin protects against lung allergen-induced inflammation

Abstract Recent studies suggest that the intestinal microenvironment regulate lung immune cells. Conversely, changes in can modulate gut system. Yet, mucosal-associated responses have been studied a compartmentalized manner, as if there is no communication between different organs. Thus, role of gut-lung axis mucosal poorly understood. Using enterotoxigenic Escherichia coli (ETEC), we established model intestine-localized infection without translocation to any other tissue. In response ETEC, type 2 innate lymphoid cells (ILC2s) and eosinophils accumulated lamina propria, even after bacterial clearance. addition, oral ETEC transiently increased numbers ILC2 parenchyma. To test promote allergen, exposed mice recently cleared intranasal papain/ovalbumin allergy induction model. Unexpectedly, ETEC-exposed were significantly resistant allergen-induced inflammation, with reduced number ILC2, Type effector CD4 +T (Th2) eosinophils. Paradoxically, ETEC-induced protection against allergen exposure was dependent on IL-33: IL-33KO developed partial inflammation this model, induced by observed. Importantly, from achieved heat-labile toxin (LT) exposure; also found toxicity domain LT needed for protection. Our results indicate gastrointestinal mediators (toxins) negatively onset allergic may provide novel immunological basis “hygiene hypothesis”. R01AI170649 FAPESP 2021/15185-2