Intestinal CD103+ dendritic cells are key players in the innate immune control of Cryptosporidium parvum infection in neonatal mice

• Published in: PLoS pathogens Vol. 9; no. 12; p. e1003801
• Main Authors: Lantier, Louis, Lacroix-Lamandé, Sonia, Potiron, Laurent, Metton, Coralie, Drouet, Françoise, Guesdon, William, Gnahoui-David, Audrey, Le Vern, Yves, Deriaud, Edith, Fenis, Aurore, Rabot, Sylvie, Descamps, Amandine, Werts, Catherine, Laurent, Fabrice
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2013; Public Library of Science (PLoS)
• Subjects: Age; Age Factors; Animals; Animals, Newborn; Antigens, CD - metabolism; Cattle; Cell research; Chemokines; Child; Cryptosporidiosis - immunology; Cryptosporidium; Cryptosporidium parvum - immunology; Dendritic cells; Dendritic Cells - metabolism; Dendritic Cells - physiology; Diarrhea; Experiments; Flow cytometry; Health aspects; Host-parasite relationships; Humans; Immune response; Immune system; Immunity, Innate; Infections; Integrin alpha Chains - metabolism; Intestines - cytology; Intestines - immunology; Life Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology and Parasitology; Parasites; Physiological aspects; Rodents; Small intestine; Zoonoses; France; Animals, Newborn; Intestines; Dendritic Cells; Age Factors; Humans; Mice, Inbred C57BL; Immunity, Innate; Mice, Knockout; Cryptosporidiosis; Animals; Cryptosporidium parvum; Cattle; Mice; Integrin alpha Chains; Child; Antigens, CD
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003801

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.