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首页> 外文期刊>Infection and immunity >The Relative Susceptibility of Mouse Strains to Pulmonary Cryptococcus neoformans Infection Is Associated with Pleiotropic Differences in the Immune Response
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The Relative Susceptibility of Mouse Strains to Pulmonary Cryptococcus neoformans Infection Is Associated with Pleiotropic Differences in the Immune Response

机译：小鼠菌株对肺隐隐球菌感染的相对易感性与免疫反应中的多效性差异有关。

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CBA/J mice were highly susceptible to intratracheal (i.t.) Cryptococcus neoformans infection relative to BALB/c mice, while both strains were equally susceptible to intravenous (i.v.) infection. Increased susceptibility in i.t. infection was associated with higher brain CFU, lower serum immunoglobulin M (IgM) and IgG responses to glucuronoxylomannan (GXM), lack of IgE regulation during infection, and alveolar macrophage permissiveness to intracellular replication in vitro. In contrast, for BALB/c mice, relative resistance was associated with increased interleukin-12 (IL-12) and decreased IL-10 pulmonary levels. In CBA/J mice, relative susceptibility was associated with a decreased proportion of CD4+ and CD8+ T cells and an increase in macrophage percentage in pulmonary infiltrates. In contrast, no significant differences in these cytokines or cell recruitment were observed in the i.v. model, consistent with no differences in the survival rate. Passive antibody (Ab) protection experiments revealed a prozone effect in the BALB/c mice with i.v. infection, such that Ab efficacy decreased at higher doses. In the i.t. model using CBA/J mice, low Ab doses were disease enhancing and protection was observed only at high doses. Our results show (i) that differences in mouse strain susceptibility are a function of the infection model, (ii) that susceptibility to pulmonary infection was associated with macrophage permissiveness for intracellular replication, and (iii) that the efficacy of passive Ab in pulmonary infection is a function of dose and mouse strain. The results highlight significant differences in the pathogenesis of cryptococcal infection among inbred mice and associate their relative susceptibility with differences in numerous components of the innate and adaptive immune responses.
机译：与BALB / c小鼠相比，CBA / J小鼠对气管内（i.t.）新型隐球菌感染高度敏感，而两种品系同样对静脉（i.v.）感染敏感。易感性增加感染与较高的脑CFU，较低的血清免疫球蛋白M（IgM）和对葡糖醛酸羟甘露聚糖（GXM）的IgG反应，感染期间缺乏IgE调节以及肺泡巨噬细胞对体外细胞内复制的允许有关。相反，对于BALB / c小鼠，相对抗性与白介素12（IL-12）升高和IL-10肺水平降低相关。在CBA / J小鼠中，相对易感性与CD4 + 和CD8 + T细胞比例降低以及肺浸润中巨噬细胞百分比升高有关。相反，在静脉内注射中未观察到这些细胞因子或细胞募集的显着差异。模型，存活率无差异。被动抗体（Ab）保护实验揭示了静脉注射BALB / c小鼠对prozone的作用。感染，使得高剂量的Ab功效降低。在i.t.在使用CBA / J小鼠的模型中，低Ab剂量会增强疾病，仅在高剂量时才观察到保护作用。我们的研究结果表明：（i）小鼠品系敏感性的差异是感染模型的函数;（ii）肺部感染的敏感性与巨噬细胞对细胞内复制的容忍度有关;（iii）被动抗体在肺部感染中的功效是剂量和小鼠劳损的函数。结果突出显示近交小鼠之间隐球菌感染的发病机制存在显着差异，并将其相对易感性与先天性和适应性免疫反应的许多组成部分的差异联系起来。

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