Wang B, Ruiz N, Pentland A, Caparon M
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Infect Immun. 1997 Jun;65(6):2119-26. doi: 10.1128/iai.65.6.2119-2126.1997.
The gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of a wide variety of suppurative infections of cutaneous tissues. Previous analyses have demonstrated that the M protein of S. pyogenes is an adhesin that directs the attachment of the streptococcus to keratinocytes in the skin. In this study, we have examined keratinocyte function in response to S. pyogenes and found that adherent versus nonadherent streptococci promote distinct patterns of expression of several proinflammatory molecules and keratinocyte cell fate. When analyzed by a quantitative reverse transcriptase PCR method, infection of cultured HaCaT keratinocytes with adherent, but not nonadherent, streptococci resulted in increased expression of mRNA for the cytokines interleukin-1alpha (IL-1alpha), IL-1beta, and IL-8 but neither infection induced expression of tumor necrosis factor alpha. In contrast, both adherent and nonadherent S. pyogenes induced expression of IL-6 and each promoted synthesis and release of prostaglandin E2 (PGE2). However, considerably greater levels of IL-6 expression were stimulated by adherent streptococci relative to nonadherent streptococci and the kinetics of PGE2 release in response to nonadherent streptococci was delayed compared to the response to adherent streptococci. Staining with the fluorescent probe ethidium homodimer-1 revealed that keratinocyte membranes were rapidly damaged upon infection with adherent streptococci but were not damaged by nonadherent streptococci. Finally, treatments which inhibited streptococcal metabolism completely blocked the ability of adherent streptococci to elicit responses. These data suggest that expression of an adhesin is a strategy used by S. pyogenes to modulate keratinocyte responses during infection of the skin and implicate additional streptococcal products in these signaling interactions.
革兰氏阳性细菌化脓性链球菌（A组链球菌）是多种皮肤组织化脓性感染的病原体。先前的分析表明，化脓性链球菌的M蛋白是一种粘附素，可引导链球菌附着于皮肤中的角质形成细胞。在本研究中，我们检测了角质形成细胞对化脓性链球菌的反应功能，发现粘附型与非粘附型链球菌可促进几种促炎分子表达的不同模式以及角质形成细胞的细胞命运。通过定量逆转录酶PCR方法分析时，用粘附型而非非粘附型链球菌感染培养的HaCaT角质形成细胞，会导致细胞因子白细胞介素-1α（IL-1α）、IL-1β和IL-8的mRNA表达增加，但两种感染均未诱导肿瘤坏死因子α的表达。相比之下，粘附型和非粘附型化脓性链球菌均诱导IL-6的表达，且每种都促进前列腺素E2（PGE2）的合成与释放。然而，相对于非粘附型链球菌，粘附型链球菌刺激的IL-6表达水平要高得多，并且与对粘附型链球菌的反应相比，对非粘附型链球菌反应的PGE2释放动力学有所延迟。用荧光探针乙锭同二聚体-1染色显示，用粘附型链球菌感染后角质形成细胞膜会迅速受损，但非粘附型链球菌不会造成损伤。最后，抑制链球菌代谢的处理完全阻断了粘附型链球菌引发反应的能力。这些数据表明，粘附素的表达是化脓性链球菌在皮肤感染期间调节角质形成细胞反应所采用的一种策略，并表明在这些信号相互作用中还涉及其他链球菌产物。
