Intestinal CD103+ Dendritic Cells Are Key Players in the Innate Immune Control of Cryptosporidium parvum Infection in Neonatal Mice

Cryptosporidium parvum is a zoonotic protozoan parasite found worldwide,that develops only in the gastrointestinal epithelium and causes profuse diarrhea. using a mouse model of c. parvum infection,we demonstrated by conditional depletion of cd11c+ cells that these cells are essential for the control of the infection both in neonates and adults. neonates are highly susceptible to c. parvum but the infection is self-limited,whereas adults are resistant unless immunocompromised. we investigated the contribution of dc to the age-dependent susceptibility to infection. we found that neonates presented a marked deficit in intestinal cd103+ dc during the first weeks of life,before weaning,due to weak production of chemokines by neonatal intestinal epithelial cells (iec). increasing the number of intestinal cd103+ dc in neonates by administering flt3-l significantly reduced susceptibility to the infection. during infections in neonates,the clearance of the parasite was preceded by a rapid recruitment of cd103+ dc mediated by cxcr3-binding chemokines produced by iec in response to ifnγ. in addition to this key role in cd103+ dc recruitment,ifnγ is known to inhibit intracellular parasite development. we demonstrated that during neonatal infection cd103+ dc produce il-12 and ifnγ in the lamina propria and the draining lymph nodes. thus,cd103+dc are key players in the innate immune control of c. parvum infection in the intestinal epithelium. the relative paucity of cd103+ dc in the neonatal intestine contributes to the high susceptibility to intestinal infection. © 2013 lantier et al.