Intestinal CD103+ dendritic cells are key players in the innate immune control of [i]Cryptosporidium parvum[/i] infection in neonatal mice
2013
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 | Infectiologie et Santé Publique (UMR ISP) ; Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT) | Régulation Immunitaire et Vaccinologie ; Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) | Centre d'Immunologie de Marseille - Luminy (CIML) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB) ; Institut Pasteur [Paris] (IP) | INRA; ICSA, the French Carnot Institute for Animal Health; EMMA service under the EU of the EC FP7 Capacities Specific Programme [227490]; Region Centre | European Project: 227490,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2008-1,EMMASERVICE(2009)
International audience
Show more [+] Less [-]English. 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 IFN gamma. In addition to this key role in CD103+ DC recruitment, IFN gamma is known to inhibit intracellular parasite development. We demonstrated that during neonatal infection CD103+ DC produce IL-12 and IFN gamma 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.
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