Protection from lethal gram-positive infection by macrophage scavenger receptor-dependent phagocytosis.
Protection from lethal gram-positive infection by macrophage scavenger receptor-dependent phagocytosis.
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巨噬细胞清道夫受体依赖性吞噬作用保护致命革兰氏阳性感染。
DOI：
10.1084/jem.191.1.147
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发表时间：
2000-01-03
期刊：
影响因子：
--
通讯作者：
El Khoury J
中科院分区：
文献类型：
--
作者：
Thomas CA;Li Y;Kodama T;Suzuki H;Silverstein SC;El Khoury J
感染革兰氏阳性细菌是人类发病和死亡的主要原因。调理素依赖的吞噬作用在预防革兰氏阳性感染和从感染中恢复方面发挥着重要作用。吞噬细胞在调理素生成和/或识别方面的先天和后天缺陷与细菌感染的易感性增加有关。相比之下，调理素非依赖性吞噬作用的生理意义尚不清楚。I型和II型A类清道夫受体(SR-AI/II)识别多种聚阴离子，包括细菌细胞壁产物，如脂多糖(LPS)和脂磷壁酸(LTA)，提示SR-AI/II在细菌感染的先天免疫中发挥作用。在这里，我们发现SR-AI/II缺陷小鼠(Msr-A−/−)比Msr-A+/+对照小鼠更容易感染典型的革兰氏阳性病原体金黄色葡萄球菌。Msr-A−/−小鼠表现出从感染部位清除细菌的能力受损，尽管中性粒细胞正常杀死金黄色葡萄球菌，并因播散性感染而死亡。Msr-A−/−巨噬细胞对革兰氏阳性细菌的调理非依赖性吞噬能力显著降低，尽管其吞噬机制完好无损。对照组小鼠的腹膜巨噬细胞以SR-AI/II依赖的方式吞噬多种革兰氏阳性细菌。我们的发现表明，SR-AI/II介导了革兰氏阳性细菌的调理素非依赖性吞噬作用，并首次提供了证据，表明调理素非依赖性吞噬作用在宿主体内抵御细菌感染中起着关键作用。
Infections with gram-positive bacteria are a major cause of morbidity and mortality in humans. Opsonin-dependent phagocytosis plays a major role in protection against and recovery from gram-positive infections. Inborn and acquired defects in opsonin generation and/or recognition by phagocytes are associated with an increased susceptibility to bacterial infections. In contrast, the physiological significance of opsonin-independent phagocytosis is unknown. Type I and II class A scavenger receptors (SR-AI/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), suggesting a role for SR-AI/II in innate immunity to bacterial infections. Here, we show that SR-AI/II–deficient mice (MSR-A−/−) are more susceptible to intraperitoneal infection with a prototypic gram-positive pathogen, Staphylococcus aureus, than MSR-A+/+ control mice. MSR-A−/− mice display an impaired ability to clear bacteria from the site of infection despite normal killing of S. aureus by neutrophils and die as a result of disseminated infection. Opsonin-independent phagocytosis of gram-positive bacteria by MSR-A−/− macrophages is significantly decreased although their phagocytic machinery is intact. Peritoneal macrophages from control mice phagocytose a variety of gram-positive bacteria in an SR-AI/II–dependent manner. Our findings demonstrate that SR-AI/II mediate opsonin-independent phagocytosis of gram-positive bacteria, and provide the first evidence that opsonin-independent phagocytosis plays a critical role in host defense against bacterial infections in vivo.
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影响因子：
64.8
作者：
BRILES, DE;CLAFLIN, JL;FORMAN, C
通讯作者：
FORMAN, C
DOI：
10.1084/jem.22.4.466
发表时间：
1915-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bull, C G
通讯作者：
Bull, C G
影响因子：
64.8
作者：
HAMPTON, RY;GOLENBOCK, DT;RAETZ, CRH
通讯作者：
RAETZ, CRH
DOI：
10.1164/ajrccm.154.3.8810595
发表时间：
1996-09-01
影响因子：
24.7
作者：
BrunBuisson, C;Doyon, F;Lepoutre, A
通讯作者：
Lepoutre, A
影响因子：
3.8
作者：
Irie, H;Koyama, H;Hill, T
通讯作者：
Hill, T