Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions.
Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions.
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DOI：
10.1038/srep26748
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发表时间：
2016-05-27
影响因子：
4.6
通讯作者：
Valentin-Weigand P
中科院分区：
文献类型：
--
作者：
Meng F;Wu NH;Seitz M;Herrler G;Valentin-Weigand P
链球菌可在气道和其他进入部位的上皮上定植。虽然局部感染通常无症状，但当链球菌侵入并扩散到受感染宿主的不同部位时，就会发生严重甚至致命的疾病。我们已经建立了猪呼吸道气液界面培养（ALI）从猪肺，以分析链球菌与其主要靶细胞的相互作用。作为链球菌家族的代表，我们选择猪链球菌（S. suis），其不仅是主要的猪呼吸道病原体，而且还可以感染人类。溶血素是一种胆固醇依赖性溶细胞素（CDC），是一种重要的毒力因子。通过比较S.在具有猪溶素缺陷突变体的猪野生型菌株中，我们证明猪溶素有助于（i）对气道细胞的粘附（ii）纤毛细胞的损失（iii）凋亡和（iv）侵袭。此外，我们表明，溶猪素的细胞溶解活性是至关重要的这些影响。我们分析的一个显著结果是S.在ALI条件下感染后，suis诱导的细胞凋亡和侵袭。据报道，当用永生化细胞分析时，这些性质的效率较低。我们假设，可溶性效应物，如suilysin是目前在更高的浓度在细胞保持在ALI条件，因此更有效。这些结果也应该与其他呼吸道病原体引起的呼吸道感染有关。
Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens.