Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis.
Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis.
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DOI：
10.1371/journal.pone.0006854
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发表时间：
2009-09-03
期刊：
影响因子：
3.7
通讯作者：
Wormley FL
中科院分区：
文献类型：
--
作者：
Wozniak KL;Ravi S;Macias S;Young ML;Olszewski MA;Steele C;Wormley FL
新型隐球菌是一种机会性真菌病原体，可在免疫功能低下的个体中引起危及生命的肺炎和脑膜脑炎。先前的研究表明，用产生 IFN-γ 的新型隐球菌菌株 H99γ 对 BALB/c 小鼠进行免疫，可以完全保护其免受致命的隐球菌菌株的第二次肺部攻击。目前的研究评估了用新型隐球菌菌株 H99γ 免疫的小鼠与用热灭活的新型隐球菌 (HKC.n.) 免疫的小鼠相比，局部记忆细胞介导的针对肺隐球菌病的免疫反应。与用 HKC.n 免疫的小鼠相比，用新型隐球菌菌株 H99γ 免疫的小鼠在二次攻击后显着降低了肺部真菌负荷。对肺隐球菌病的保护作用与肺部肉芽肿形成和白细胞浸润增加有关，随后肺部炎症迅速消退，从而保护肺部免受严重过敏性支气管肺真菌病（ABPM）的影响，这种病理学是在用 HKC.n 免疫的小鼠肺部发生的。用新型隐球菌菌株 H99γ 对白细胞介素 (IL)-4 受体、IL-12p40、IL-12p35、IFN-γ、T 细胞和 B 细胞缺陷小鼠进行肺部攻击，结果表明需要 Th1 型 T 细胞介导的免疫，而不是 B 细胞介导的免疫，才能诱导 H99γ 介导的针对肺部新型隐球菌感染的保护性免疫应答。受保护的小鼠中，CD4+ T 细胞、CD11c+ 细胞和 Gr-1+ 细胞的比例和绝对数量均增加。此外，在受保护小鼠的肺部观察到 Th1 型/促炎细胞因子和趋化因子的产生显着增加，相反，Th2 型细胞因子的产生减少。有趣的是，保护与受保护小鼠肺部细胞因子 IFN-γ 或 TNF-α 的产生增加无关。总之，用新型隐球菌菌株 H99γ 进行免疫会导致保护性抗隐球菌免疫反应的发展，该免疫反应可被测量并随后用于开发基于免疫的疗法来对抗肺隐球菌病。
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-γ-producing C. neoformans strain, H99γ, results in complete protection against a second pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against pulmonary cryptococcosis in mice immunized with C. neoformans strain H99γ compared to mice immunized with heat-killed C. neoformans (HKC.n.). Mice immunized with C. neoformans strain H99γ had significantly reduced pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against pulmonary cryptococcosis was associated with increased pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of pulmonary inflammation, which protected the lungs from severe allergic bronchopulmonary mycosis (ABPM)-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL)-4 receptor, IL-12p40, IL-12p35, IFN-γ, T cell and B cell deficient mice with C. neoformans strain H99γ demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99γ-mediated protective immune responses against pulmonary C. neoformans infection. CD4+ T cells, CD11c+ cells, and Gr-1+ cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-γ or TNF-α in lungs of protected mice. In conclusion, immunization with C. neoformans strain H99γ results in the development of protective anti-cryptococcal immune responses that may be measured and subsequently used in the development of immune-based therapies to combat pulmonary cryptococcosis.
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影响因子：
3.1
作者：
Huang, C;Nong, SH;Levitz, SM
通讯作者：
Levitz, SM
影响因子：
3.1
作者：
Herring, AC;Lee, J;Huffnagle, GB
通讯作者：
Huffnagle, GB
影响因子：
3.1
作者：
Cox, GM;Mukherjee, J;Perfect, JR
通讯作者：
Perfect, JR
影响因子：
3.1
作者：
BLASI, E;MAZZOLLA, R;BISTONI, F
通讯作者：
BISTONI, F
DOI：
10.1084/jem.173.3.755
发表时间：
1991-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hill JO;Harmsen AG
通讯作者：
Harmsen AG