Liévin-Le Moal Vanessa, Servin Alain L, Coconnier-Polter Marie-Hélène
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 510, Pathogènes et Fonctions des Cellules Epithéliales Polarisées, Faculté de Pharmacie Paris XI, F-92296 Châtenay-Malabry, France.
Cell Microbiol. 2005 Jul;7(7):1035-48. doi: 10.1111/j.1462-5822.2005.00532.x.
In vivo Listeria monocytogenes infection results in the massive release of mucus by goblet cells into the lumen of the intestine. We have previously reported that apical infection by L. monocytogenes is followed by listeriolysin O (LLO)-dependent stimulation of mucus exocytosis, and the upregulation of the MUC genes. Here, we report that L. monocytogenes EGD wild-type bacteria enter cultured human polarized, mucin-secreting, HT29-MTX cells apically by an InlA-dependent mechanism. The LLO-induced increase in mucin secretion together with an increase in transcription of the MCU4 and MUC12 genes encoding for membrane-bound mucins, results in the inhibition of the cell-entry of L. monocytogenes into mucin-secreting, HT29-MTX cells. Moreover, we report that sialic acid residues in mucins are crucial for the inhibition of L. monocytogenes internalization. Based on these findings, we suggest that the LLO-induced mucin exocytosis and upregulation of the MUC genes encoding for membrane-bound mucins constitute a host cell defence response that inhibits the cell-entry of L. monocytogenes.
体内单核细胞增生李斯特菌感染导致杯状细胞向肠腔大量分泌黏液。我们之前报道过,单核细胞增生李斯特菌顶端感染后会引发依赖李斯特菌溶血素O(LLO)的黏液分泌胞吐作用刺激,以及MUC基因的上调。在此,我们报道单核细胞增生李斯特菌EGD野生型细菌通过依赖内化素A(InlA)的机制顶端进入培养的人极化、分泌黏蛋白的HT29-MTX细胞。LLO诱导的黏蛋白分泌增加以及编码膜结合黏蛋白的MCU4和MUC12基因转录增加,导致单核细胞增生李斯特菌进入分泌黏蛋白的HT29-MTX细胞的细胞内吞作用受到抑制。此外,我们报道黏蛋白中的唾液酸残基对于抑制单核细胞增生李斯特菌内化至关重要。基于这些发现,我们认为LLO诱导的黏蛋白胞吐作用以及编码膜结合黏蛋白的MUC基因上调构成了一种宿主细胞防御反应,可抑制单核细胞增生李斯特菌的细胞内吞作用。