Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages
Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages
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DOI：
10.1016/j.jiac.2015.08.001
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发表时间：
2015-12-01
影响因子：
2.2
通讯作者：
Miyazaki, Yoshitsugu
中科院分区：
文献类型：
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作者：
Ikeda-Dantsuji, Yurika;Ohno, Hideaki;Miyazaki, Yoshitsugu
在侵袭性真菌感染中，由吸入新型隐球菌或加蒂隐球菌引起的隐球菌病特别危险，因为它可以传播到中枢神经系统，引起危及生命的脑膜炎或脑膜脑炎。先前的报道描述了新生C.和C. gatii感染的组织病理学特征的显著差异，例如C. gatii感染的小鼠肺部更大的病原体增殖和有限的巨噬细胞反应。为了阐明这两种隐球菌的致病性差异，我们利用激光共聚焦显微镜研究了新生隐球菌和加蒂隐球菌与宿主第一道防线巨噬细胞的相互作用。巨噬细胞只吞噬薄包膜的新生C.和非厚包膜的C. gatii。干扰素-g预激活可使薄包膜新生梭菌的吞噬率提高两倍，但对薄包膜加蒂梭菌的吞噬没有促进作用。脂多糖预活化或烟曲霉分生菌共孵育对巨噬细胞对薄包膜新生弧菌和加蒂弧菌的内化没有影响。活的薄包膜新生C.虫的吞噬作用诱导巨噬细胞释放白细胞介素-12，而活的薄包膜加蒂C.虫没有。然而，热杀死或多聚甲醛固定的薄胶囊新生酵母的吞噬并没有增加IL-12的释放，这表明在新生酵母-巨噬细胞相互作用期间，活酵母的内化对于启动免疫应答很重要。我们的数据表明巨噬细胞对C. gatti的反应与对C.新生C. gatti的反应相比是有限的，这些结果可能部分解释了C. gatti有限的免疫反应和更大的致病性。(c) 2015年，日本化疗学会和日本传染病协会。Elsevier Ltd.出版。版权所有。
Among invasive fungal infections, cryptococcosis caused by inhalation of Cryptococcus neoformans or Cryptococcus gattii is particularly dangerous because it can disseminate to the central nervous system and cause life-threatening meningitis or meningoencephalitis. Previous reports described significant differences in the histopathological features of C. neoformans and C. gattii infection, such as greater pathogen proliferation and a limited macrophage response in mouse lung infected by C. gattii. To elucidate the difference in pathogenicity of these two Cryptococcus species, we investigated the interaction of C. neoformans and C. gattii with murine macrophages, the first line of host defense, by confocal laser microscopy. Only thin-capsulated, and not thick-capsulated C. neoformans and C. gattii were phagocytosed by macrophages. Preactivation with interferon-g increased the phagocytic rate of thin-capsulated C. neoformans up to two-fold, but did not promote phagocytosis of thin- capsulated C. gattii. Lipopolysaccharide preactivation or Aspergillus fumigatus conidia co-incubation had no effect on internalization of thin-capsulated C. neoformans or C. gattii by macrophages. Phagocytosis of live thin-capsulated C. neoformans, but not that of live thin-capsulated C. gattii, induced interleukin-12 release from macrophages. However, phagocytosis of heat-killed or paraformaldehyde-fixed thin-capsulated C. neoformans did not increase IL-12 release, showing that the internalization of live yeast is important for initiating the immune response during C. neoformans-macrophage interactions. Our data suggest that macrophage response to C. gattii is limited compared with that to C. neoformans and that these results may partially explain the limited immune response and the greater pathogenicity of C. gattii. (c) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.