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Cryptosporidium parvum subverts the host innate immune response through manipulation of CRAMP expression during neonatal infection

Abstract : Due to the immaturity of their immune system, neonates are highly sensitive to intestinal infections. During the neonatal period, antimicrobial peptide (AMP) expression differs substantially from that of adults as this is the case for the cathelicidin-related antimicrobial peptide CRAMP expressed preferentially in the neonatal period while conversely other AMPs such as Reg3c are expressed later in life. Among enteric neonatal diseases, Cryptosporidiosis is a zoonotic disease and is highly prevalent in in young infant less than 5 years old in underdeveloped country and in neonatal ruminants worldwide. Cryptosporidium parvum is the etiological agent of this diarrheal disease and infects exclusively epithelial cells. Innate immunity is important to control the acute phase of infection in neonates with dendritic cells and IFNc playing a major role. Antimicrobial peptides are important contributors of innate immunity, but the role of CRAMP, which is elevated in the intestine of neonates has never been investigated during Cryptosporidiosis so far. In this work, we used the neonatal murine model of cryptosporidiosis and unlike all the other antimicrobial peptides analyzed CRAMP expression in the intestinal epithelial cells was significantly reduced during infection. This reduced CRAMP expression is independent of IFNg, a cytokine strongly produced during infection but also Myd88 and gut flora independent. When C. parvum infected neonatal mice orally received exogenous CRAMP to compensate the reduced expression of this AMP, the parasitic load of neonates was significantly decreased. In addition, when free parasites were in direct contact with CRAMP, this AMP affects the viability of sporozoites, the first free infectious form of this parasite. All together, these data suggest that C. parvum induces the reduction of CRAMP expression to escape the anti-parasiticidal effect of CRAMP. The molecular mechanism by which the parasite subverts epithelialderived CRAMP production is currently under investigation.
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Déposant : Migration Prodinra <>
Soumis le : mercredi 3 juin 2020 - 06:28:42
Dernière modification le : mardi 11 août 2020 - 15:10:04


  • HAL Id : hal-02743750, version 1
  • PRODINRA : 277423
  • WOS : 000343733800038



William Guesdon, Tiffany Pézier, Françoise Drouet, Sandrine Ménard, Fabrice Laurent, et al.. Cryptosporidium parvum subverts the host innate immune response through manipulation of CRAMP expression during neonatal infection. 9. European Mucosal Immunology Group Meeting, Oct 2014, Glasgow, United Kingdom. John Wiley and Sons, Ltd., Immunology, 143, 2014. ⟨hal-02743750⟩



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