Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling
Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling
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DOI：
10.1111/j.1462-5822.2005.00525.x
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Wessels, MR
中科院分区：
文献类型：
--
作者：
Bentley, CC;Hakansson, A;Wessels, MR
A 族链球菌 (GAS) 定植于口咽部和受损皮肤。为了引起局部感染或严重的侵袭性综合症，细菌必须进入更深的组织。宿主细胞死亡可能促进这一过程。 GAS 内化已被证实可诱导细胞凋亡。我们现在报道了 GAS 介导的原代人角质形成细胞凋亡的另一种机制，该机制由细胞外 GAS 启动并涉及细胞内钙失调以产生内质网应激。细胞外 GAS 有效诱导细胞凋亡需要两种细菌毒力因子：(i) 透明质酸胶囊，抑制细菌内化；(ii) 分泌型溶细胞素，链球菌溶血素 O (SLO)，形成跨膜孔，允许细胞外钙流入细胞质。野生型 GAS 诱导角质形成细胞凋亡伴随着细胞脱离和上皮完整性丧失，而胶囊或 SLO 缺陷的 GAS 则未观察到这种现象。我们认为，细胞外 GAS 启动的细胞信号传导通过诱导角质形成细胞过早分化和凋亡来损害上皮屏障，从而促进 GAS 侵入更深的组织。
Group A Streptococcus (GAS) colonizes the oropharynx and damaged skin. To cause local infection or severe invasive syndromes the bacteria must gain access into deeper tissues. Host cell death may facilitate this process. GAS internalization has been identified to induce apoptosis. We now report an alternate mechanism of GAS-mediated apoptosis of primary human keratinocytes, initiated by extracellular GAS and involving dysregulation of intracellular calcium to produce endoplasmic reticulum stress. Two bacterial virulence factors are required for effective induction of apoptosis by extracellular GAS: (i) hyaluronic acid capsule that inhibits bacterial internalization and (ii) secreted cytolysin, streptolysin O (SLO), that forms transmembrane pores that permit extracellular calcium influx into the cytosol. Induction of keratinocyte apoptosis by wild-type GAS was accompanied by cell detachment and loss of epithelial integrity, a phenomenon not observed with GAS deficient in capsule or SLO. We propose that cell signalling initiated by extracellular GAS compromises the epithelial barrier by inducing premature keratinocyte differentiation and apoptosis, thereby facilitating GAS invasion of deeper tissues.