新型隐球菌的细胞表面蛋白介导哺乳动物细胞的粘附和内化

Q4 Medicine
K. Choo, V. Chin, P. Chong, S. H. Ho, V. Yong
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引用次数: 0

摘要

新型隐球菌是一种封装的真菌病原体,主要在免疫功能低下的患者中引起严重疾病。微生物病原体在宿主细胞中的粘附和内化通常始于微生物与宿主表面受体的结合。然而,对所涉及的机制仍知之甚少。在这项研究中,我们研究了新生隐球菌细胞表面决定簇与哺乳动物细胞的关系。我们的结果表明,用胰蛋白酶处理,而不是用多聚甲醛或热杀,减少了宿主与隐球菌的相互作用,这表明新生隐球菌的细胞表面蛋白(CSP)参与了这种相互作用。我们通过提取新生隐球菌的CSP并将其偶联到乳胶珠上,扩展了我们的研究,以确定CSP在隐球菌-宿主细胞相互作用中的作用。CSP与包膜和非包膜新生隐球菌的结合增加了乳胶珠与哺乳动物肺泡上皮细胞、肺泡巨噬细胞和单核细胞衍生的巨噬细胞的结合。对宿主细胞肌动蛋白组织的进一步检查表明,肌动蛋白依赖性吞噬作用参与了CSP偶联乳胶珠中新生隐球菌的内化。我们假设存在于新生隐球菌细胞壁上的CSP介导哺乳动物细胞对隐球菌的粘附和肌动蛋白依赖性吞噬作用。我们的研究结果值得进一步研究CSP在隐球菌病发病机制中的确切作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CELL SURFACE PROTEINS OF CRYPTOCOCCUS NEOFORMANS MEDIATE ADHERENCE AND INTERNALISATION INTO MAMMALIAN CELLS
Cryptococcus neoformans is an encapsulated fungal pathogen that caused severe disease primarily in immunocompromised patients. Adherence and internalization of microbial pathogens into host cells are often begin with engagement of microbes to the surface receptors of host. However, the mechanisms involved remain poorly understood. In this study, we investigated association of cell surface determinants of C. neoformans with mammalian cells. Our results showed that treatment with trypsin, but not paraformaldehyde or heat killing, has reduced host-cryptococci interaction, suggesting the involvement of cell surface proteins (CSPs) of C. neoformans in this interaction. We extended our investigations to determine roles of CSPs during cryptococci-host cells interaction by extracting and conjugating CSPs of C. neoformans to latex beads. Conjugation of CSPs with both encapsulated and acapsular C. neoformans increased the association of latex beads with mammalian alveolar epithelial cells, alveolar macrophages and monocyte-derived macrophages. Further examination on the actin organisation of the host cells implied the involvement of actin-dependent phagocytosis in the internalisation of C. neoformans in CSP-conjugated latex beads. We hypothesized that CSPs present on the cell wall of C. neoformans mediate the adherence and actin-dependent phagocytosis of cryptococci by mammalian cells. Our results warrant further studies on the exact role of CSPs in pathogenesis during cryptococcosis.
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