Cytolysins augment superantigen penetration of stratified mucosa.
Cytolysins augment superantigen penetration of stratified mucosa.
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细胞素蛋白增强分层粘膜的超抗原渗透。
DOI：
10.4049/jimmunol.0803283
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发表时间：
2009-02-15
期刊：
影响因子：
--
通讯作者：
Schlievert PM
中科院分区：
文献类型：
--
作者：
Brosnahan AJ;Mantz MJ;Squier CA;Peterson ML;Schlievert PM
金黄色葡萄球菌和化脓性链球菌定植于人体粘膜表面引起疾病。这两种微生物都产生了一组称为超抗原的毒力因子，这使得它们能够从身体的阴道（葡萄球菌）或口腔粘膜（链球菌）引起严重的疾病。超抗原与T细胞和抗原呈递细胞相互作用，引起大量细胞因子释放，介导统称为中毒性休克综合征的症状。在这里，我们证明了另一组毒力因子，溶细胞素，帮助超抗原穿透阴道粘膜作为一个代表性的非角化复层鳞状上皮表面。在超抗原穿透的离体模型中，葡萄球菌溶细胞素α毒素和链球菌溶细胞素O分别增强了中毒性休克综合征毒素-1和链球菌致热原外毒素A穿过猪阴道粘膜的穿透。在组织学检查时，两种溶细胞素均对阴道组织的最上层造成损伤。使用永生化人阴道上皮细胞的体外证据表明，尽管两种超抗原都是促炎性的，但只有葡萄球菌溶细胞素α毒素诱导细胞产生强烈的免疫应答。链球菌溶血素O迅速破坏并杀死细胞，仅允许少量白细胞介素-1 β释放。提出了两种不同的超抗原渗透模型：葡萄球菌α毒素诱导上皮细胞产生强烈的促炎反应，破坏粘膜，足以增强中毒性休克综合征毒素-1的渗透，而链球菌溶血素O直接损伤粘膜，使链球菌致热外毒素A和可能的活链球菌渗透。
Staphylococcus aureus and Streptococcus pyogenes colonize mucosal surfaces of the human body to cause disease. A group of virulence factors known as superantigens are produced by both of these organisms, which allows them to cause serious diseases from the vaginal (staphylococci) or oral mucosa (streptococci) of the body. Superantigens interact with T cells and antigen presenting cells to cause massive cytokine release to mediate the symptoms collectively known as toxic shock syndrome. Here we demonstrate that another group of virulence factors, cytolysins, aid in the penetration of superantigens across vaginal mucosa as a representative nonkeratinized stratified squamous epithelial surface. The staphylococcal cytolysin α toxin and the streptococcal cytolysin streptolysin O enhanced penetration of toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, respectively, across porcine vaginal mucosa in an ex vivo model of superantigen penetration. Upon histological examination, both cytolysins caused damage to the uppermost layers of the vaginal tissue. In vitro evidence using immortalized human vaginal epithelial cells demonstrated that although both superantigens were proinflammatory, only the staphylococcal cytolysin α toxin induced a strong immune response from the cells. Streptolysin O damaged and killed the cells quickly, allowing only a small release of interleukin-1β. Two separate models of superantigen penetration are proposed: staphylococcal α toxin induces a strong proinflammatory response from epithelial cells to disrupt the mucosa enough to allow for enhanced penetration of toxic shock syndrome toxin-1, whereas streptolysin O directly damages the mucosa to allow for penetration of streptococcal pyrogenic exotoxin A and possibly viable streptococci.
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DOI：
10.1016/s0002-9378(03)00873-1
发表时间：
2003-12-01
影响因子：
9.8
作者：
Davis, CC;Kremer, MJ;Squier, CA
通讯作者：
Squier, CA
影响因子：
11.8
作者：
Kravitz, GR;Dries, DJ;Schlievert, PM
通讯作者：
Schlievert, PM
影响因子：
11.8
作者：
Eschenbach, DA;Thwin, SS;Stamm, WE
通讯作者：
Stamm, WE
影响因子：
82.9
作者：
Kotb, M;Norrby-Teglund, A;Low, DE
通讯作者：
Low, DE
DOI：
10.1007/bf00330426
发表时间：
1987-06-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
KREISWIRTH, BN;HANDLEY, JP;NOVICK, RP
通讯作者：
NOVICK, RP