Schindler Ben, Segal Esther
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Med Mycol. 2008 May;46(3):251-8. doi: 10.1080/13693780701837157.
Candida albicans is the most common opportunistic fungal pathogen of humans, causing systemic disease in immunocompromised patients. Host resistance to C. albicans infections is mediated predominantly by neutrophils and monocytes/macrophages. We have previously shown that exposure of a human epithelial cell line (HEp2) to C. albicans or to a culture filtrate of C. albicans caused actin rearrangement in the HEp2 cells. Since shifting of actin from the filamentous to the globular form may be crucial to the activity of phagocytes, we assessed in the present study the effect of the C. albicans metabolite (lyophilized culture filtrate) on the cytoskeleton of murine peritoneal macrophages and on their phagocytic activity. Our results showed a significant decrease in phagocytosis of C. albicans, ranging from 53-63% and a 25% reduction for C. glabrata cells. Using confocal laser scanning microscopy an actin rearrangement in the macrophages could be demonstrated that may be associated with the decrease of phagocytosis. We also tested the effect of mannan and of the secreted aspartic proteinase (Sap) inhibitor--pepstatin, on the activity of the metabolite in order to define the putative component and found no influence. In conclusion, our data indicate that a C. albicans metabolite affects phagocytic activity of macrophages, probably by alterations in their cytoskeleton.
白色念珠菌是人类最常见的机会性真菌病原体,可在免疫功能低下的患者中引起全身性疾病。宿主对白色念珠菌感染的抵抗力主要由中性粒细胞和单核细胞/巨噬细胞介导。我们之前已经表明,将人上皮细胞系(HEp2)暴露于白色念珠菌或白色念珠菌的培养滤液中会导致HEp2细胞中的肌动蛋白重排。由于肌动蛋白从丝状形式转变为球状形式可能对吞噬细胞的活性至关重要,因此我们在本研究中评估了白色念珠菌代谢产物(冻干培养滤液)对小鼠腹膜巨噬细胞细胞骨架及其吞噬活性的影响。我们的结果显示,白色念珠菌的吞噬作用显著降低,范围为53%-63%,光滑念珠菌细胞的吞噬作用降低了25%。使用共聚焦激光扫描显微镜可以证明巨噬细胞中的肌动蛋白重排,这可能与吞噬作用的降低有关。我们还测试了甘露聚糖和分泌天冬氨酸蛋白酶(Sap)抑制剂——胃蛋白酶抑制剂对代谢产物活性的影响,以确定推定成分,但未发现有影响。总之,我们的数据表明,白色念珠菌代谢产物可能通过改变巨噬细胞的细胞骨架来影响其吞噬活性。