α-Toxin Facilitates the Generation of CXC Chemokine Gradients and Stimulates Neutrophil Homing in Staphylococcus aureus Pneumonia
α-Toxin Facilitates the Generation of CXC Chemokine Gradients and Stimulates Neutrophil Homing in Staphylococcus aureus Pneumonia
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DOI：
10.1086/592758
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发表时间：
2008-11-15
影响因子：
6.4
通讯作者：
Park, Pyong Woo
中科院分区：
文献类型：
--
作者：
Bartlett, Allison H.;Foster, Timothy J.;Park, Pyong Woo
背景资料。金黄色葡萄球菌α毒素是金黄色葡萄球菌的主要毒力因子，但其体内作用机制尚不完全清楚。我们用金黄色葡萄球菌8325-4株(Hla(+)金黄色葡萄球菌)和以8325-4为背景的α毒素缺乏突变株(Hla(+)金黄色葡萄球菌)建立小鼠鼻腔肺部感染模型，研究了α毒素在金黄色葡萄球菌肺炎中的作用。与感染Hla(+)金黄色葡萄球菌的小鼠相比，经鼻感染Hla(+)金黄色葡萄球菌的小鼠的肺损伤和炎症、肺水肿和组织细菌负荷显著减少。此外，与感染Hla(+)金黄色葡萄球菌的小鼠相比，感染Hla(+)金黄色葡萄球菌的小鼠死于感染的人数较少。感染Hla(+)金黄色葡萄球菌的小鼠呼吸道中CXC趋化因子、角质形成细胞源性趋化因子和巨噬细胞炎性蛋白-2水平显著降低，这种差异是新合成的趋化因子向呼吸道分泌减少的结果。与这些数据一致的是，感染Hla(+)金黄色葡萄球菌的小鼠与感染Hla(+)金黄色葡萄球菌的小鼠相比，呼吸道和肺中的中性粒细胞明显减少。这些数据表明，α-毒素通过促进CXC趋化因子梯度的产生和刺激趋化因子诱导的中性粒细胞在金黄色葡萄球菌肺炎中的流入而增强毒力。
Background. Staphylococcus aureus alpha-toxin is a major virulence factor, but its mechanism of action in vivo is incompletely understood.Methods. We examined the role of alpha-toxin in S. aureus pneumonia using the mouse model of intranasal lung infection with S. aureus strain 8325-4 (hla(+) S. aureus) and an alpha-toxin-deficient mutant strain made on the 8325-4 background (hla(+) S. aureus).Results. Intranasal infection of mice with hla(+) S. aureus resulted in substantially less lung injury and inflammation, pulmonary edema, and tissue bacterial burden than did infection with hla(+) S. aureus. Furthermore, fewer mice infected with hla(+) S. aureus died of the infection, compared with those infected with hla(+) S. aureus. Levels of the CXC chemokines keratinocyte-derived chemokine and macrophage inflammatory protein-2 were significantly lower in the airways of mice infected with hla(+) S. aureus, and this difference was the result of reduced secretion of newly synthesized chemokines into the airway. Consistent with these data, significantly fewer neutrophils were present in the airways and lungs of mice infected with hla(+) S. aureus, compared with those infected with hla(+) S. aureus.Conclusions. These data suggest that alpha-toxin enhances virulence by facilitating the generation of CXC chemokine gradients and stimulating chemokine-induced neutrophil influx in S. aureus pneumonia.