Saccharomyces cerevisiae Expressing Gp43 Protects Mice against Paracoccidioides brasiliensis Infection

Saccharomyces cerevisiae Expressing Gp43 Protects Mice against Paracoccidioides brasiliensis Infection
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DOI:
10.1371/journal.pone.0120201
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发表时间:
2015-03-19
期刊:
影响因子:
3.7
通讯作者:
Rodrigues Coelho, Paulo Sergio
Rodrigues Coelho, Paulo Sergio
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Assis-Marques, Mariana Aprigio;Oliveira, Aline Ferreira;Rodrigues Coelho, Paulo Sergio

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巴西副球孢子菌(Paracoccidioides brasiliensis)是副球孢子菌病(Paracoccidioidomycosis,PCM)的病原菌。据信,大约有1000万人感染了这种真菌,大约2%的人最终会患上这种疾病。与病毒和细菌疾病不同,真菌疾病是没有商业疫苗的疾病。酿酒酵母可能是用于针对真菌感染的免疫的合适媒介物,因为它们需要刺激免疫应答的不同分支。本研究采用S.表达gp 43的酿酒酵母。当通过接种巴西假单胞菌酵母进行攻击时,免疫动物在三种不同的测定中显示出保护性特征。它们的肺实质被显著地保留,表现出比未免疫小鼠更少的肉芽肿和更少的真菌细胞。免疫小鼠的肺和脾中的真菌负荷减少,并且两个器官都含有较高水平的IL-12和IFN-γ。与未接种疫苗的小鼠相比,这一发现表明Th 1免疫的发生。综上所述,我们的结果表明,重组酵母疫苗代表了一种新的策略,赋予对PCM的保护。
The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM). It is believed that approximately 10 million people are infected with the fungus and approximately 2% will eventually develop the disease. Unlike viral and bacterial diseases, fungal diseases are the ones against which there is no commercially available vaccine. Saccharomyces cerevisiae may be a suitable vehicle for immunization against fungal infections, as they require the stimulation of different arms of the immune response. Here we evaluated the efficacy of immunizing mice against PCM by using S. cerevisiae yeast expressing gp43. When challenged by inoculation of P. brasiliensis yeasts, immunized animals showed a protective profile in three different assays. Their lung parenchyma was significantly preserved, exhibiting fewer granulomas with fewer fungal cells than found in non-immunized mice. Fungal burden was reduced in the lung and spleen of immunized mice, and both organs contained higher levels of IL-12 and IFN-gamma. compared to those of non-vaccinated mice, a finding that suggests the occurrence of Th1 immunity. Taken together, our results indicate that the recombinant yeast vaccine represents a new strategy to confer protection against PCM.