The Glycosylphosphatidylinositol-Anchored Protease Sap9 Modulates the Interaction of Candida albicans with Human Neutrophils
The Glycosylphosphatidylinositol-Anchored Protease Sap9 Modulates the Interaction of Candida albicans with Human Neutrophils
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DOI：
10.1128/iai.00723-09
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
Kurzai, Oliver
中科院分区：
文献类型：
--
作者：
Hornbach, Anke;Heyken, Antje;Kurzai, Oliver
人类多形核中性粒细胞（PMNs）在抵抗侵袭性白念珠菌感染的免疫防御中起主要作用。这种真菌病原体产生一组天冬氨酸蛋白酶，直接有助于毒力特性，如粘附，组织入侵和免疫逃避。我们发现，与其他分泌型蛋白酶相比，细胞表面相关的同种型Sap 9对C.白念珠菌的PMN。SAP 9是诱导PMN向C.白念珠菌丝，有效的PMN激活的必要先决条件。此外，SAP 9的缺失导致人PMN中活性氧中间体（ROI）的释放减轻，并降低C。白色念珠菌诱导的细胞凋亡由ROI形成触发。在对抗试验中，与野生型C相比，SAP 9缺失突变体的杀伤减少。白色念珠菌这些数据清楚地暗示了Sap 9蛋白酶活性在保护性先天免疫的启动中的作用，并提示了C.白色念珠菌-宿主相互作用导致嗜中性粒细胞活化。
Human polymorphonuclear neutrophils (PMNs) play a major role in the immune defense against invasive Candida albicans infection. This fungal pathogen produces a set of aspartic proteases that directly contributes to virulence properties such as adhesion, tissue invasion, and immune evasion. We show here that, in contrast to other secreted proteases, the cell surface-associated isoform Sap9 has a major impact on the recognition of C. albicans by PMNs. SAP9 is required for the induction of PMN chemotaxis toward C. albicans filaments, an essential prerequisite of effective PMN activation. Furthermore, deletion of SAP9 leads to a mitigated release of reactive oxygen intermediates (ROI) in human PMNs and decreases C. albicans-induced apoptosis triggered by ROI formation. In confrontation assays, killing of a SAP9 deletion mutant is reduced in comparison to wild-type C. albicans. These data clearly implicate Sap9 protease activity in the initiation of protective innate immunity and suggest novel molecular mechanisms in C. albicans-host interaction leading to neutrophil activation.