SPECIFIC SUSCEPTIBILITY TO MUCORMYCOSIS IN MURINE DIABETES AND BRONCHOALVEOLAR MACROPHAGE DEFENSE AGAINST RHIZOPUS
SPECIFIC SUSCEPTIBILITY TO MUCORMYCOSIS IN MURINE DIABETES AND BRONCHOALVEOLAR MACROPHAGE DEFENSE AGAINST RHIZOPUS
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DOI：
10.1172/jci111395
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
DIAMOND, RD
中科院分区：
文献类型：
--
作者：
WALDORF, AR;RUDERMAN, N;DIAMOND, RD
用链脲佐菌素诱导的小鼠糖尿病模型评估糖尿病对肺毛霉菌病易感性的影响。在糖尿病小鼠中鼻腔接种米曲霉可导致毛霉菌感染，其组织病理学与在人类中观察到的肺毛霉病相似。接种正常小鼠无一例死亡，无感染。糖尿病小鼠有由米曲霉引起的致命感染，但接种烟曲霉菌后死亡率显著降低。这些发现反映了在人类糖尿病患者中观察到的毛霉菌病的特殊增强的易感性。正常的支气管肺泡巨噬细胞通过抑制发芽形成对稻瘟病菌的有效防御的一部分，发芽是稻瘟病菌转化为组织侵袭期的关键步骤。支气管肺泡巨噬细胞在体外抑制孢子萌发，并似乎有助于阻止体内萌发。糖尿病小鼠鼻腔接种后出现孢子萌发。糖尿病患者的肺泡巨噬细胞附着菌丝的能力降低。在糖尿病小鼠中，支气管肺泡巨噬细胞可以破坏稻瘟病菌的孢子或菌丝，但血清因素似乎既促进了孢子萌发，又损害了巨噬细胞与孢子的附着。这种小鼠糖尿病模型为评价细胞和血清介导的宿主因素在毛霉菌病发病机制中的相对重要性提供了机会。
The influence of diabetes mellitus in predisposing to pulmonary mucormycosis was assessed using a murine model of streptozotocin-induced diabetes. Intranasal inoculation of R. oryzae into diabetic mice resulted in mucormycotic infection with histopathology resembling pulmonary mucormycosis observed in humans. There was no mortality nor infection in inoculated normal mice. Diabetic mice had fatal infections caused by R. oryzae but significantly reduced mortality following inoculation with Aspergillus fumigatus. These findings reflect the specific enhanced susceptibility to mucormycosis observed in human diabetics. Normal bronchoalveolar macrophages formed part of an efficient defense against R. oryzae by inhibiting germination, the critical step in the conversion of R. oryzae to its tissue invasive phase. Bronchoalveolar macrophages inhibited spore germination in vitro and appeared to help prevent germination in vivo. Spore germination occurred in diabetic mice following intranasal inoculation. Diabetic bronchoalveolar macrophages had a decreased ability to attach to hyphae. In diabetic mice, bronchoalveolar macrophages could damage spores or hyphae of R. oryzae, but serum factors appeared to both promote spore germination and impair attachment of macrophages to spores. This murine model of diabetes mellitus provides an opportunity for evaluation of the relative importance of cell and serum-mediated host factors in the pathogenesis of mucormycosis.