Identification and characterization of Cryptococcus neoformans protein fractions that induce protective immune responses.
Identification and characterization of Cryptococcus neoformans protein fractions that induce protective immune responses.
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DOI：
10.1002/pmic.201300213
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发表时间：
2013-12
期刊：
影响因子：
3.4
通讯作者：
Wormley, Floyd L., Jr.
中科院分区：
文献类型：
--
作者：
Chaturvedi, Ashok K.;Weintraub, Susan T.;Lopez-Ribot, Jose L.;Wormley, Floyd L., Jr.
关键词：
新型隐球菌是隐球菌病的主要病原体，是一种真菌病原体，可在免疫功能低下的患者中引起危及生命的脑膜脑炎。迄今为止，还没有批准用于治疗隐球菌病的疫苗或免疫疗法。细胞和抗体介导的免疫反应协同调节针对新型隐球菌感染的最佳保护。因此，我们鉴定了能够刺激细胞和抗体介导的免疫反应的隐球菌蛋白片段，并确定了它们对隐球菌病产生保护作用的功效。从新型隐球菌中提取蛋白质并根据分子量进行分级。然后通过免疫印迹分析评估这些级分对保护性免疫小鼠提取的血清的反应性，并通过细胞因子回忆测定评估其诱导与保护相关的促炎和 Th1 型细胞因子反应的功效。质谱分析揭示了许多在应激反应、信号转导、碳水化合物代谢、氨基酸合成和蛋白质合成中发挥作用的蛋白质。使用含有免疫显性抗原的精选蛋白组分进行免疫可显着延长实验性肺隐球菌病的存活时间。我们的研究支持结合使用免疫学和蛋白质组学方法来鉴定能够引发抗原特异性抗体和 Th1 型细胞因子反应的蛋白质。所发现的免疫显性抗原代表了开发用于治疗和/或预防隐球菌病的新型亚单位疫苗的有吸引力的候选者。
Cryptococcus neoformans , the main causative agent of cryptococcosis, is a fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. To date, there is no vaccine or immunotherapy approved to treat cryptococcosis. Cell- and antibody-mediated immune responses collaborate to mediate optimal protection against C. neoformans infections. Accordingly, we identified cryptococcal protein fractions capable of stimulating cell- and antibody-mediated immune responses and determined their efficacy to elicit protection against cryptococcosis. Proteins were extracted from C. neoformans and fractionated based on molecular mass. The fractions were then evaluated by immunoblot analysis for reactivity to serum extracted from protectively immunized mice and in cytokine recall assays for their efficacy to induce pro-inflammatory and Th1-type cytokine responses associated with protection. Mass spectrometry analysis revealed a number of proteins with roles in stress response, signal transduction, carbohydrate metabolism, amino acid synthesis, and protein synthesis. Immunization with select protein fractions containing immunodominant antigens induced significantly prolonged survival against experimental pulmonary cryptococcosis. Our studies support using the combination of immunological and proteomic approaches to identify proteins that elicit antigen-specific antibody and Th1-type cytokine responses. The immunodominant antigens that were discovered represent attractive candidates for the development of novel subunit vaccines for treatment and/or prevention of cryptococcosis.
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影响因子：
39.2
作者：
GOLDSTEIN, E;RAMBO, ON
通讯作者：
RAMBO, ON
影响因子：
3.1
作者：
Deepe, GS;Gibbons, RS
通讯作者：
Gibbons, RS
影响因子：
6.7
作者：
Cowen LE
通讯作者：
Cowen LE
影响因子：
6.4
作者：
DROMER, F;CHARREIRE, J
通讯作者：
CHARREIRE, J
影响因子：
5.2
作者：
Feldmesser, M;Mukherjee, J;Casadevall, A
通讯作者：
Casadevall, A