Panepinto John C, Komperda Kazimierz W, Hacham Moshe, Shin Soowan, Liu Xiaoguang, Williamson Peter R
University of Illinois at Chicago, Section of Infectious Diseases, Chicago, IL 60612, USA.
Infect Immun. 2007 Oct;75(10):4769-79. doi: 10.1128/IAI.00536-07. Epub 2007 Jul 23.
Mannan binding lectin (MBL) is an innate immune mediator belonging to the collectin family known to bind to the surfaces of many viruses, bacteria, and fungi. However, pathogenic strains of the fungus Cryptococcus neoformans are resistant to MBL binding. To dissect the mechanism of cryptococcal resistance to MBL, we compared MBL binding to an encapsulated wild-type strain, an encapsulated ccr4Delta mutant defective in cell integrity, and an acapsular cap60Delta strain. No MBL binding was detected on wild-type C. neoformans. In contrast, the ccr4Delta mutant bound MBL to the cell wall, predominantly at the ends of enlarged buds, whereas the acapsular strain bound MBL only at the bud neck and bud scars. In addition, the ccr4Delta mutant was sensitive to the cell wall-active antifungal caspofungin and other cell wall stress inducers, and its virulence was reduced in a mouse model of cryptococcosis. Interestingly, treatment of wild-type cells with caspofungin also increased MBL binding to C. neoformans. These results suggest that both the presence of capsule and wild-type cell wall architecture preclude MBL binding to C. neoformans.
甘露聚糖结合凝集素（MBL）是一种先天性免疫介质，属于胶原凝集素家族，已知可与许多病毒、细菌和真菌的表面结合。然而，新型隐球菌的致病菌株对MBL结合具有抗性。为了剖析隐球菌对MBL的抗性机制，我们比较了MBL与一株有荚膜野生型菌株、一株细胞完整性存在缺陷的有荚膜ccr4Δ突变体以及一株无荚膜cap60Δ菌株的结合情况。在野生型新型隐球菌上未检测到MBL结合。相比之下，ccr4Δ突变体将MBL结合到细胞壁上，主要在增大芽体的末端，而无荚膜菌株仅在芽颈和芽痕处结合MBL。此外，ccr4Δ突变体对细胞壁活性抗真菌药物卡泊芬净和其他细胞壁应激诱导剂敏感，并且在隐球菌病小鼠模型中其毒力降低。有趣的是，用卡泊芬净处理野生型细胞也增加了MBL与新型隐球菌的结合。这些结果表明，荚膜的存在和野生型细胞壁结构均会阻止MBL与新型隐球菌结合。
