Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Cell Host Microbe. 2010 Jan 21;7(1):38-49. doi: 10.1016/j.chom.2009.12.008.
IL-1beta produced by phagocytes is important for protection against the mucosal pathogen Staphylococcus aureus. Processing and maturation of this cytokine requires activation of the multiprotein inflammasome complex. We observed that the bacterial cell wall component peptidoglycan (PGN) must be particulate and internalized via phagocytosis to activate NLRP3 inflammasomes and IL-1beta secretion. In the context of S. aureus infection of macrophages, we find that phagocytosis and lysozyme-based bacterial cell wall degradation are necessary to induce IL-1beta secretion. Further, an S. aureus enzyme, PGN O-acetyltransferase A, previously demonstrated to make cell wall PGN resistant to lysozyme, strongly suppresses inflammasome activation and inflammation in vitro and in vivo. These observations demonstrate that phagocytosis and lysozyme-based cell wall degradation of S. aureus are functionally coupled to inflammasome activation and IL-1beta secretion and illustrate a case whereby a bacterium specifically subverts IL-1beta secretion through chemical modification of its cell wall PGN.
吞噬细胞产生的白细胞介素-1β对于抵抗黏膜病原体金黄色葡萄球菌非常重要。这种细胞因子的加工和成熟需要多蛋白炎症小体复合物的激活。我们观察到，细菌细胞壁成分肽聚糖（PGN）必须是颗粒状的，并通过吞噬作用内化，才能激活 NLRP3 炎症小体并分泌白细胞介素-1β。在金黄色葡萄球菌感染巨噬细胞的情况下，我们发现吞噬作用和溶菌酶介导的细菌细胞壁降解对于诱导白细胞介素-1β分泌是必要的。此外，金黄色葡萄球菌的一种酶，PGN O-乙酰转移酶 A，先前被证明使细胞壁 PGN 对溶菌酶具有抗性，它强烈抑制炎症小体的激活和体内外炎症反应。这些观察结果表明，金黄色葡萄球菌的吞噬作用和溶菌酶介导的细胞壁降解与炎症小体的激活和白细胞介素-1β的分泌功能相关联，并说明了一种情况，即细菌通过化学修饰其细胞壁 PGN 特异性地下调白细胞介素-1β的分泌。
