Guesdon William, Auray Gaël, Pezier Tiffany, Bussière Françoise I, Drouet Françoise, Le Vern Yves, Marquis Mathilde, Potiron Laurent, Rabot Sylvie, Bruneau Aurelia, Werts Catherine, Laurent Fabrice, Lacroix-Lamandé Sonia
INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly Université François Rabelais, UMR1282 Infectiologie et Santé Publique, Tours.
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.
J Infect Dis. 2015 Oct 15;212(8):1332-40. doi: 10.1093/infdis/jiv206. Epub 2015 Apr 2.
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.
CCL20是一种具有抗菌活性的趋化因子。我们研究了其在新生儿隐孢子虫病（一种导致严重腹泻的全球性原生动物肠道疾病）期间的表达及作用。令人惊讶的是，在感染微小隐孢子虫期间，新生小鼠肠道产生CCL20的过程通过一种既不依赖肠道菌群也不依赖干扰素γ（解决这种感染的关键细胞因子）的机制而减少。然而，给新生小鼠口服重组CCL20可通过一种不依赖免疫细胞募集的机制显著降低寄生虫载量，这种机制是通过对寄生虫游离阶段的直接溶细胞活性实现的。MiR21在功能上靶向CCL20且在感染期间上调，从而导致趋化因子的下调。我们的研究结果首次证明了CCL20对肠道原生动物的直接抗寄生虫活性及其在微小隐孢子虫感染期间的下调，这不利于寄生虫的清除。
