Soluble CD163 promotes recognition, phagocytosis and killing of Staphylococcus aureus via binding of specific fibronectin peptides
Soluble CD163 promotes recognition, phagocytosis and killing of Staphylococcus aureus via binding of specific fibronectin peptides
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DOI：
10.1111/j.1462-5822.2012.01766.x
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发表时间：
2012-06-01
影响因子：
3.4
通讯作者：
Barczyk, Katarzyna
中科院分区：
文献类型：
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作者：
Kneidl, Jessica;Loeffler, Bettina;Barczyk, Katarzyna
CD163是一种由单核细胞和巨噬细胞特异表达的多配体清道夫受体，在脓毒症时被激活后释放(SCD163)。然而，sCD163的生物学相关性尚不清楚。我们现在证明了sCD163通过识别与葡萄球菌表面分子结合的纤维连接蛋白(FN)的特定亚片段(6F11F22F27F1)而显示出直接的抗菌作用。此外，与葡萄球菌的接触通过诱导金属蛋白酶ADAM10和ADAM17促进sCD163从单核细胞表面脱落。随后，sCD163通过FN多肽与金黄色葡萄球菌结合，并强烈增强单核细胞的吞噬和杀伤作用，中性粒细胞的作用较弱。这一机制表现出额外的旁分泌作用，因为sCD163额外调理的葡萄球菌诱导了更高的激活和更有效的对内皮细胞等非专业吞噬细胞的杀伤活性。用sCD163靶向病原体结合的Fn将是攻击金黄色葡萄球菌的一种非常复杂的策略，因为病原体任何试图避开这种防御机制的尝试都会自动导致与宿主蛋白Fn的黏附丧失，这是高侵袭性葡萄球菌菌株的关键致病机制。因此，我们报道了sCD163的一个新功能，它对于宿主对金黄色葡萄球菌感染的免疫防御具有特别重要的作用。
CD163 is a multi-ligand scavenger receptor exclusively expressed by monocytes and macrophages, which is released after their activation during sepsis (sCD163). The biological relevance of sCD163, however, is not yet clear. We now demonstrate that sCD163 exhibits direct antimicrobial effects by recognizing a specific subfragment (6F11F22F27F1) of fibronectin (FN) bound to staphylococcal surface molecules. Moreover, contact with staphylococci promotes sCD163-shedding from monocyte surface via induction of metalloproteinases ADAM10 and ADAM17. sCD163 subsequently binds to Staphylococcus aureus via FN peptides and strongly amplifies phagocytosis as well as killing by monocytes and to a lesser extend by neutrophils. This mechanism exhibits additional paracrine effects because staphylococci additionally opsonized by sCD163 induce higher activation and more efficient killing activity of non-professional phagocytes like endothelial cells. Targeting pathogen-bound FN by sCD163 would be a very sophisticated strategy to attack S. aureus as any attempt of the pathogen to avoid this defence mechanism will automatically bring about loss of adherence to the host protein FN, which is a pivotal patho-mechanism of highly invasive staphylococcal strains. Thus, we report a novel function for sCD163 that is of particular importance for immune defence of the host against S. aureus infections.