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CD103+DC play a key role in the innate immune mechanisms protecting the epithelium against neonatal enteric infections

Abstract : Neonates are generally more susceptible than adults to infectious diseases. Their intestinal immune system is in development and subject to numerous changes after birth, facing the colonization by the commensal flora, alimentary antigens, and aggression by enteric pathogens. Cryptosporidium parvum is a highly prevalent zoonotic protozoan parasite that develops only in the gastrointestinal epithelium and causes profuse diarrhea that can be life threatening in very young children and immunocompromised individuals. Neonatal mice are highly susceptible to C. parvum but the infection is self-limited, whereas adult mice are resistant unless immunocompromised. Accumulating evidences obtained with the neonatal mouse model demonstrate the key role of innate immunity to control the acute phase of the infection. Conditional depletion of CD11c+ cells demonstrated their essential role for the control of the infection both in neonates and adults (1). We therefore investigated the contribution of CD103+ DC to the age-dependent susceptibility to infection. We found that neonates presented a marked deficit in CD103+ DC in the intestinal lamina propria during the first weeks of life and artificially increasing the number of intestinal CD103+ DC by administering FLT3-L significantly reduced susceptibility to the infection. We next identified an unexpected mechanism of recruitment of the CD103+ DC during the infection with several transgenic mouse models. Indeed, rapid recruitment of CD103+ DC was depending on the production of CXCR3-binding chemokines produced by IEC in response to IFN . In addition to this key role in CD103+ DC recruitment, IFN is known to inhibit intracellular parasite development. We demonstrated that during neonatal infection CD103+ DC produce IL-12 and IFN 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. Our work makes a substantial increase in the understanding of the role of immune effectors involved in the control of the acute phase of C. parvum infection and paves the way to immune modulation strategies (2) targeting intestinal DC for strengthening neonatal immune system against enteric infections. (1) Lantier et al. PLoS Pathog. 2013 (2) Lantier et al. J Infect Dis. 2014 KW Dendritic Neonate Innate Infection
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https://hal.inrae.fr/hal-02738636
Déposant : Migration Prodinra <>
Soumis le : mardi 2 juin 2020 - 21:04:49
Dernière modification le : jeudi 16 juillet 2020 - 15:36:06

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  • HAL Id : hal-02738636, version 1
  • PRODINRA : 277433
  • WOS : 000343733800049

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Fabrice Laurent, Louis Lantier, Sonia Lacroix Lamandé, Françoise Drouet, William Guesdon, et al.. CD103+DC play a key role in the innate immune mechanisms protecting the epithelium against neonatal enteric infections. 9. European Mucosal Immunology Group Meeting, Oct 2014, Glasgow, United Kingdom. John Wiley and Sons, Ltd., Immunology, 143, 42 p., 2014. ⟨hal-02738636⟩

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