title: CCL20 Displays Antimicrobial Activity Against Cryptosporidium parvum, but Its Expression Is Reduced During Infection in the Intestine of Neonatal Mice.
abstract: CCL20 is a chemokine with antimicrobial activity. We investigated its expression and role during neonatal cryptosporidiosis, a worldwide protozoan enteric disease leading to severe diarrhea. Surprisingly, during infection by Cryptosporidium parvum, CCL20 production by the intestine of neonatal mice is reduced by a mechanism independent both of the enteric flora and of interferon γ, a key cytokine for the resolution of this infection. However, oral administration of recombinant CCL20 to neonatal mice significantly reduced the parasite load by a mechanism that was independent of immune cell recruitment and occurred instead by direct cytolytic activity on free stages of the parasite. MiR21 functionally targets CCL20 and is upregulated during the infection, thus contributing to the downregulation of the chemokine. Our findings demonstrate for the first time the direct antiparasitic activity of CCL20 against an enteric protozoan and its downregulation during C. parvum infection, which is detrimental to parasite clearance.
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: William
authors.initials: W
authors.lastname: Guesdon
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Gaël
authors.initials: G
authors.lastname: Auray
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Pezier
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Françoise I
authors.initials: FI
authors.lastname: Bussière
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Françoise
authors.initials: F
authors.lastname: Drouet
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours INRA Val de Loire, Cytometry Platform.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Vern
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Marquis
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Laurent
authors.initials: L
authors.lastname: Potiron
authors.affiliation: INRA, UMR1319 Micalis AgroParisTech, UMR Micalis, Jouy-en-Josas.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rabot
authors.affiliation: INRA, UMR1319 Micalis AgroParisTech, UMR Micalis, Jouy-en-Josas.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Bruneau
authors.affiliation: Unité Biologie et Génétique de la Paroi Bactérienne, Institut Pasteur, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Werts
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Laurent
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lacroix-Lamandé
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000890:Anti-Infective Agents / Q000378:metabolism*; D002460:Cell Line; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D034101:Sporozoites
chemical_list: D000890:Anti-Infective Agents; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D011994:Recombinant Proteins; D007371:Interferon-gamma
keywords: CCL20; Cryptosporidium parvum; antimicrobial activity; chemokine; neonatal mice