Early Life Infection Withcryptosporidium Parvuminduces Inflammatory Responses to Dietary Antigens

SummaryTo examine the effect of early-life infection withCryptosporidium parvumon the development of oral tolerance, we developed a low-dose infection model in neonatal mice.C. parvuminfection in neonatal mice results in immunopathology in the colon. IL-1β released duringC. parvuminfection 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 withC. parvum, adoptively transferred OT-II cells, which respond to ovalbumin (ova), developed reduced frequency of Foxp3+Rorγt+cells in mesenteric lymph nodes with an expansion of TH1-like Tregs in the colon. 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 development leads to loss of oral tolerance during early life infection withC. parvum.