Effects of immune suppression in murine models of disseminated Candida glabrata and Candida tropicalis infection and utility of a synthetic peptide vaccine.
Effects of immune suppression in murine models of disseminated Candida glabrata and Candida tropicalis infection and utility of a synthetic peptide vaccine.
复制标题
免疫抑制对播散性光滑念珠菌和热带念珠菌感染的小鼠模型的影响以及合成肽疫苗的效用。
DOI：
10.1093/mmy/myy122
复制
发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Xin,Hong
中科院分区：
文献类型：
--
作者：
Xin,Hong
真菌是全球真菌感染的第二大常见原因。目前对念珠菌免疫的认识几乎完全来自于对白色念珠菌的研究，白色念珠菌是最常见的致病菌。由于缺乏可用于研究这些重要病原体的动物模型，对白念珠菌（NAC）的免疫学认识仍处于早期阶段。这部分是因为许多NAC物种在念珠菌病小鼠模型中通常不是致病性的。在本研究中，我们建立了一种免疫抑制的小鼠播散性念珠菌病模型。glabrata和C.近交系小鼠A/J和BALB/c对播散性疟原虫感染表现出明显的易感性。缺乏补体C5的A/J小鼠更容易受到这两种C的播散性感染。glabrata和C.与BALB/c小鼠相比，后者具有功能性C5。在这里，我们表明，肽脉冲的树突状细胞（DC）与来自aC的肽接种。Tropicaliscell表面蛋白，显着提高了生存率，并减少了这些免疫功能低下的小鼠播散性念珠菌病的真菌负担。重要的是，这项研究是第一次报告的保护效力赋予肽疫苗对医学上重要的NAC物种在免疫抑制的主机。该实验模型的建立为进一步了解病毒感染的发病机制和宿主抗性提供了重要工具。值得注意的是，我们的研究结果还表明，该模型可用于评估新的念珠菌病控制策略，如疫苗。
Candidaspecies are the second most frequent cause of fungal infections worldwide. Current knowledge of immunity toCandidahas been gleaned almost exclusively from studies onCandida albicans, the most common disease-causing species. Knowledge of immunity tonon-albicans Candida (NAC)species is still at an early stage due to the lack of tractable animal models with which to study these important pathogens. This is partly because manyNACspecies are not usually pathogenic in mouse models of candidiasis. In this study, we established an immunosuppressed mouse model of disseminated candidiasis by the two clinically importantNACspecies, C. glabrata and C. tropicalis.The inbred mouse strains, A/J and BALB/c, show distinct susceptibilities to disseminatedCandidainfection. A/J mice, deficient for complement C5, are more susceptible to disseminated infection with bothC. glabrataandC. tropicaliscompared to BALB/c mice, the latter having functional C5. Here we show that peptide-pulsed dendritic cell (DC) vaccination with a peptide derived from aC. tropicaliscell surface protein, significantly improved survival and reduced the fungal burdens of disseminated candidiasis in these immunocompromised mice. Importantly, this study is the first report of protective efficacy conferred by a peptide vaccine against medically important NAC species in immunosuppressed hosts. Establishing this experimental mouse model provides an important tool to further understand pathogenesis and host resistance inCandidainfection. Significantly, our findings also demonstrate how this model can be used to evaluate new control strategies against candidiasis, such as vaccines.