<i>Cryptosporidium parvum</i> Subverts Antimicrobial Activity of CRAMP by Reducing Its Expression in Neonatal Mice

• Main Authors: William Guesdon, Tiffany Pezier, Sandrine Menard, Alessandra Nicolosi, Yves Le Vern, Anne Silvestre, Julien Diana, Fabrice Laurent, Sonia Lacroix-Lamandé
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Microorganisms
• Subjects: <i>Cryptosporidium parvum</i>; CRAMP; antimicrobial activity; neonatal mice
• Online Access: https://www.mdpi.com/2076-2607/8/11/1635

<i>Cryptosporidium parvum</i> causes diarrhea in infants under 5 years, in immunosuppressed individuals or in young ruminants. This parasite infects the apical side of ileal epithelial cells where it develops itself and induces inflammation. Antimicrobial peptides (AMPs) are part of the innate immune response, playing a major role in the control of the acute phase of <i>C. parvum</i> infection in neonates. Intestinal AMP production in neonates is characterized by high expressions of Cathelicidin Related Antimicrobial Peptide (CRAMP), the unique cathelicidin in mice known to fight bacterial infections. In this study, we investigated the role of CRAMP during cryptosporidiosis in neonates. We demonstrated that sporozoites are sensitive to CRAMP antimicrobial activity. However, during <i>C. parvum</i> infection the intestinal expression of CRAMP was significantly and selectively reduced, while other AMPs were upregulated. Moreover, despite high CRAMP expression in the intestine of neonates at homeostasis, the depletion of CRAMP did not worsen <i>C. parvum</i> infection. This result might be explained by the rapid downregulation of CRAMP induced by infection. However, the exogenous administration of CRAMP dampened the parasite burden in neonates. Taken together these results suggest that <i>C. parvum</i> impairs the production of CRAMP to subvert the host response, and highlight exogenous cathelicidin supplements as a potential treatment strategy.