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J Infect Dis. 2015 Oct 15;212(8):1332-40. doi: 10.1093/infdis/jiv206. Epub 2015 Apr 2.

CCL20 Displays Antimicrobial Activity Against Cryptosporidium parvum, but Its Expression Is Reduced During Infection in the Intestine of Neonatal Mice.

Author information

1
INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
2
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.
3
INRA, UMR1319 Micalis AgroParisTech, UMR Micalis, Jouy-en-Josas.
4
Unité Biologie et Génétique de la Paroi Bactérienne, Institut Pasteur, Paris, France.

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.

KEYWORDS:

CCL20; Cryptosporidium parvum; antimicrobial activity; chemokine; neonatal mice

PMID:
25838265
DOI:
10.1093/infdis/jiv206
[Indexed for MEDLINE]

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