Effects of early-life infection with Cryptosporidium parvum

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-1beta 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. Adoptively transferred OT-II cells, which respond to ovalbumin (ova), developed reduced frequency of Foxp3+Rorgammat+ cells in mesenteric lymph nodes of C. parvum infected mice 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 cells lead to loss of oral tolerance during early life infection with C. parvum.