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

被引:34
作者
Guesdon, William [1 ,2 ]
Auray, Gael [1 ,2 ]
Pezier, Tiffany [1 ,2 ]
Bussiere, Francoise I. [1 ,2 ]
Drouet, Francoise [1 ,2 ]
Le Vern, Yves [1 ,2 ,3 ]
Marquis, Mathilde [1 ,2 ]
Potiron, Laurent [1 ,2 ]
Rabot, Sylvie [4 ,5 ]
Bruneau, Aurelia [4 ,5 ]
Werts, Catherine [6 ]
Laurent, Fabrice [1 ,2 ]
Lacroix-Lamande, Sonia [1 ,2 ]
机构
[1] INRA Val Loire, Infectiol & Sante Publ UMR1282, F-37380 Nouzilly, France
[2] Univ Tours, Infectiol & Sante Publ UMR1282, Tours, France
[3] INRA Val Loire, Cytometry Platform, F-37380 Nouzilly, France
[4] INRA, Micalis UMR1319, Paris, France
[5] AgroParisTech, UMR Micalis, Jouy En Josas, France
[6] Inst Pasteur, Unite Biol & Genet Paroi Bacterienne, Paris, France
关键词
Cryptosporidium parvum; CCL20; chemokine; antimicrobial activity; neonatal mice; EPITHELIAL-CELLS; GAMMA-INTERFERON; INFLAMMATORY PROTEIN-3-ALPHA/CCL20; IMMUNE-RESPONSE; GENE-EXPRESSION; CHEMOKINES; MODULATION; PROTECTION; SECRETION; APOPTOSIS;
D O I
10.1093/infdis/jiv206
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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., 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.
引用
收藏
页码:1332 / 1340
页数:9
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