Gut Microbes. 2025 Dec;17(1):2551115. doi: 10.1080/19490976.2025.2551115. Epub 2025 Aug 28.
ABSTRACT
To examine the effect of early-life infection with Cryptosporidium parvum on the development of oral tolerance, we developed a low-dose infection model in neonatal mice. C. parvum infection in neonatal mice results in immunopathology in the colon. IL-1β released during C. parvum infection blocked the formation of colonic goblet cell associated antigen passages, which normally serve as a conduit for antigen uptake and development of peripheral regulatory T cells (pTregs), responsible for long-term oral tolerance. Following infection with C. parvum, adoptively transferred OT-II cells, which respond to ovalbumin (ova, a model food antigen), underwent expansion of TH1-like Tregs in the colon while the frequency of Foxp3+Rorγt+ cells in mesenteric lymph nodes decreased. The altered pTreg profile was accompanied by a strong TH1 immune response and robust IgG2c antibody responses to orally administered ova. Our findings suggest that intestinal inflammation and altered pTreg cells lead to loss of oral tolerance during early life infection with C. parvum.
PMID:40874311 | DOI:10.1080/19490976.2025.2551115
