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

PLoS Pathogens

Edith Deriaud¹  Audrey Gnahoui-David¹  Catherine Werts¹  Françoise Drouet¹  Louis Lantier¹  Sylvie Rabot¹  Laurent Potiron¹  Amandine Descamps²  Fabrice Laurent²  Yves Le Vern²  Sonia Lacroix-Lamandé²  William Guesdon²  Aurore Fenis²  Coralie Metton² 

[1] INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France;Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France

关键词: Neonates;    Gastrointestinal tract;    Cryptosporidium parvum;    Gastrointestinal infections;    Parasitic intestinal diseases;    Parasitic diseases;    Mouse models;    Chemokines;   

DOI  :  10.1371/journal.ppat.1003801

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY