Dendritic cell-based immunization ameliorates pulmonary infection with highly virulent Cryptococcus gattii.
Dendritic cell-based immunization ameliorates pulmonary infection with highly virulent Cryptococcus gattii.
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基于树突状细胞的免疫可改善高毒力格特隐球菌的肺部感染。
DOI：
10.1128/iai.02827-14
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Y
中科院分区：
文献类型：
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作者：
Keigo Ueno;Yuki Kinjo;Yoichiro Okubo;Kyoko Aki;Makoto Urai;Yukihiro Kaneko;Kiminori Shimizu;Dan-Ni Wang;Akiko Okawara;Takuya Nara;Kayo Ohkouchi;Yuki Mizuguchi;Susumu Kawamoto;Katsuhiko Kamei;Hideaki Ohno;Yoshihito Niki;Kazutoshi Shibuya;Y
1999年，由一种剧毒真菌加特隐球菌引起的隐球菌病在加拿大温哥华岛及周边地区成为一种传染病，导致免疫能力正常的个体死亡。以往的研究表明，C.从加拿大疫情中分离出的格特病毒株R265具有免疫回避或免疫抑制能力。然而，对C. gattii尚未被确定。在这项研究中，我们使用功能获得的方法来研究对C。使用树突状细胞（DC）为基础的疫苗，骨髓来源的树突状细胞（BMDCs）有效地吞噬无囊C。gattii（Δ cap 60株），导致其表达共刺激分子和炎性细胞因子。这在用包封的菌株培养的BMDC中没有观察到。当Δ cap 60菌株脉冲的BMDCs在R265感染前转移到小鼠体内时，与对照组相比，病理学、真菌负荷和存活率显著改善。吞噬真菌细胞的多核巨细胞（MGCs）在免疫小鼠的肺中显著增加。免疫小鼠脾和肺中产生白细胞介素17 A（IL-17 A）、γ干扰素（IFN-γ）和肿瘤坏死因子α（TNF-α）的淋巴细胞显著增加。该DC疫苗在IFN-γ敲除小鼠中的保护作用显著降低。这些结果表明，产生细胞因子的淋巴细胞的增加和吞噬真菌细胞的MGCs的发育与对抗高毒力C肺部感染的保护作用有关。gattii，并建议IFN-γ可能是这种疫苗诱导的保护的重要介质。
Cryptococcosis due to a highly virulent fungus, Cryptococcus gattii, emerged as an infectious disease on Vancouver Island in Canada and surrounding areas in 1999, causing deaths among immunocompetent individuals. Previous studies indicated that C. gattii strain R265 isolated from the Canadian outbreak had immune avoidance or immune suppression capabilities. However, protective immunity against C. gattii has not been identified. In this study, we used a gain-of-function approach to investigate the protective immunity against C. gattii infection using a dendritic cell (DC)-based vaccine. Bone marrow-derived dendritic cells (BMDCs) efficiently engulfed acapsular C. gattii (Δcap60strain), which resulted in their expression of costimulatory molecules and inflammatory cytokines. This was not observed for BMDCs that were cultured with encapsulated strains. When Δcap60strain-pulsed BMDCs were transferred to mice prior to intratracheal R265 infection, significant amelioration of pathology, fungal burden, and the survival rate resulted compared with those in controls. Multinucleated giant cells (MGCs) that engulfed fungal cells were significantly increased in the lungs of immunized mice. Interleukin 17A (IL-17A)-, gamma interferon (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing lymphocytes were significantly increased in the spleens and lungs of immunized mice. The protective effect of this DC vaccine was significantly reduced in IFN-γ knockout mice. These results demonstrated that an increase in cytokine-producing lymphocytes and the development of MGCs that engulfed fungal cells were associated with the protection against pulmonary infection with highly virulent C. gattii and suggested that IFN-γ may have been an important mediator for this vaccine-induced protection.