Early life infection with <i>Cryptosporidium parvum</i> induces inflammatory responses to dietary antigens

To examine the effect of early-life infection with <i>Cryptosporidium parvum</i> on the development of oral tolerance, we developed a low-dose infection model in neonatal mice. <i>C. parvum</i> infection in neonatal mice results in immunopathology in the colon. IL-1β released during <i>C. parvum</i> 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 <i>C. parvum</i>, adoptively transferred OT-II cells, which respond to ovalbumin (ova, a model food antigen), underwent expansion of T_H1-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 T_H1 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 <i>C. parvum</i>.