Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans.
Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans.
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IFN-γ激活的巨噬细胞的杀菌活性。
DOI：
10.4049/jimmunol.142.9.3219
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发表时间：
1989
影响因子：
4.4
通讯作者：
S. Kaufmann
中科院分区：
文献类型：
--
作者：
I. Flesch;G. Schwamberger;S. Kaufmann
新型隐球菌是一种被包裹的酵母状真菌，在免疫功能低下的宿主中优先引起肺部和脑膜感染。细胞介导的免疫被认为是重要的获得性抗隐球菌病，活化的巨噬细胞作为最后的效应细胞。然而，在新曲霉的胶囊中，特定的多糖保护真菌免受吞噬细胞的粘附和随后的吞噬。我们研究了ifn - γ激活的巨噬细胞及其产物对新生C.的细胞外杀伤作用。ifn - γ刺激小鼠骨髓源性巨噬细胞24 h后，能有效抑制新生巨噬细胞的生长，且ifn - γ的作用被LPS增强。用ifn - γ + LPS刺激骨髓源性巨噬细胞的无细胞上清液也能杀死新生c。我们的研究结果表明，活化的巨噬细胞对新生c的杀伤不依赖于有毒的氧自由基，而是由表观分子质量为15和30 kDa的分泌蛋白介导的。这些发现表明，活化的巨噬细胞在宿主防御中起着重要作用，尽管真菌抵抗吞噬并留在细胞外环境中。
Cryptococcus neoformans is an encapsulated yeast-form fungus which causes pulmonary and meningeal infections preferentially in the immunocompromised host. It is thought that cell-mediated immunity is important for acquired resistance against cryptococcosis with activated macrophages as the final effector cells. However, specific polysaccharides in the capsule of C. neoformans protect the fungus from adherence to phagocytes and from subsequent phagocytosis. We have studied extracellular killing of C. neoformans by IFN-gamma-activated macrophages and their products. Murine bone marrow-derived macrophages stimulated with rIFN-gamma for 24 h were able to effectively suppress the growth of C. neoformans and the effect of IFN-gamma was augmented by LPS. Killing of C. neoformans was also achieved by cell-free supernatants from bone marrow-derived macrophages stimulated with IFN-gamma plus LPS. Our results indicate that killing of C. neoformans by activated macrophages is independent from toxic oxygen radicals and mediated by secreted protein(s) of apparent molecular mass of 15 and 30 kDa. These findings indicate that activated macrophages play a major role in host defense, although the fungus resists phagocytosis and remains in the extracellular milieu.