title: Intestinal CD103+ dendritic cells are key players in the innate immune control of Cryptosporidium parvum infection in neonatal mice.
abstract: 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.
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Lantier
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lacroix-Lamandé
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Potiron
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Metton
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Drouet
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: William
authors.initials: W
authors.lastname: Guesdon
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gnahoui-David
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Vern
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Deriaud
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université d'Aix-Marseille, Marseille, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Fenis
authors.affiliation: INRA, UMR 1319, Micalis, Jouy-en-Josas, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rabot
authors.affiliation: INRA, UMR 1319, Micalis, Jouy-en-Josas, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Descamps
authors.affiliation: Institut Pasteur, Unité de Biologie et Génétique de la Paroi Bactérienne, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Werts
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France ; Universite Francois Rabelais, UMR1282 Infectiologie et Sante Publique, Tours, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Laurent
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism*; D002417:Cattle; D002648:Child; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology*; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D039001:Integrin alpha Chains / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins