Flesch I E, Schwamberger G, Kaufmann S H
Department of Medical Microbiology and Immunology, University of Ulm, FRG.
J Immunol. 1989 May 1;142(9):3219-24.
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.
新型隐球菌是一种有荚膜的酵母样真菌，主要在免疫功能低下的宿主中引起肺部和脑膜感染。据认为，细胞介导的免疫对于获得性抗隐球菌病的抵抗力很重要，活化的巨噬细胞是最终的效应细胞。然而，新型隐球菌荚膜中的特定多糖可保护真菌不被吞噬细胞黏附以及随后的吞噬作用。我们研究了γ干扰素活化的巨噬细胞及其产物对新型隐球菌的细胞外杀伤作用。用重组γ干扰素刺激24小时的小鼠骨髓来源巨噬细胞能够有效抑制新型隐球菌的生长，并且脂多糖可增强γ干扰素的作用。用γ干扰素加脂多糖刺激的骨髓来源巨噬细胞的无细胞上清液也能实现对新型隐球菌的杀伤。我们的结果表明，活化的巨噬细胞对新型隐球菌的杀伤作用独立于毒性氧自由基，且由表观分子量为15和30 kDa的分泌蛋白介导。这些发现表明，尽管真菌能抵抗吞噬作用并保留在细胞外环境中，但活化的巨噬细胞在宿主防御中起主要作用。
