Discordant susceptibility of inbred C57BL/6 versus outbred CD1 mice to experimental fungal sepsis
Discordant susceptibility of inbred C57BL/6 versus outbred CD1 mice to experimental fungal sepsis
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DOI：
10.1111/cmi.12995
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Lozano, Francisco
中科院分区：
文献类型：
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作者：
Carreras, Esther;Velasco de Andres, Maria;Lozano, Francisco
侵袭性和/或免疫抑制医学干预后对真菌感染的个体易感性差异是重要的临床问题。为了探索可能与真菌感染易感性相关的免疫反应相关因素，我们比较了近交系C57BL/6J和近交系CD1小鼠对不同真菌脓毒症实验模型的反应。zymosan诱导的广泛性炎症模型动物的挑战显示，与CD1小鼠相比，C57BL/6J的存活率较低，与Th1细胞因子干扰素(IFN)- γ血清水平较低一致。同样，与CD1小鼠相比，C57BL/6J脾细胞离体暴露于酶酵素，也暴露于细菌脂多糖或脂壁酸，导致ifn - γ分泌减少。通过单独或联合ss-葡聚糖结合CD5蛋白（0.7 mg/kg）输注相对低剂量的ifn - γ (0.2 μ g/kg)，可以恢复C57BL/6J的易感性，从而改善酶生蛋白诱导的全身炎症存活。同样，在C57BL/6J小鼠中，低剂量ifn - γ输注可改善全身白色念珠菌感染的低生存率（2.86 x 10(4) CFU/gr），而CD1小鼠则没有。我们的研究结果强调了真菌感染实验模型中菌株选择的重要性，并为更特异性的抗真菌免疫治疗设计提供了敏感性基础。
Individual susceptibility differences to fungal infection following invasive and/or immunosuppressive medical interventions are an important clinical issue. In order to explore immune response-related factors that may be linked to fungal infection susceptibility, we have compared the response of inbred C57BL/6J and outbred CD1 mouse strains to different experimental models of fungal sepsis. The challenge of animals with the zymosan-induced generalised inflammation model revealed poorer survival rates in C57BL/6J, consistent with lower Th1 cytokine interferon (IFN)-gamma serum levels, compared with CD1 mice. Likewise, ex vivo exposure of C57BL/6J splenocytes to zymosan but also bacterial lipopolisaccharide or lipoteichoic acid, resulted in lower IFN-gamma secretion compared with CD1 mice. C57BL/6J susceptibility could be reverted by rescue infusion of relative low IFN-gamma doses (0.2 mu g/kg) either alone or in combination with the ss-glucan-binding CD5 protein (0.7 mg/kg) leading to improved post zymosan-induced generalised inflammation survival. Similarly, low survival rates to systemic Candida albicans infection (2.86 x 10(4) CFU/gr) were ameliorated by low-dose IFN-gamma infusion in C57BL/6J but not CD1 mice. Our results highlight the importance of strain choice in experimental fungal infection models and provide a susceptibility rationale for more specific antifungal immunotherapy designs.