Cole G T, Lynn K T, Seshan K R, Pope L M
Department of Botany, University of Texas, Austin.
J Med Vet Mycol. 1989;27(6):363-80. doi: 10.1080/02681218980000491.
Oral-intragastric inoculation of 6-day-old outbred Crl:CFW(SW) BR mice with Candida albicans can lead to colonization of the gastrointestinal (GI) tract. We have shown that in the absence of an immunocompromising treatment, Candida is primarily localized in the stomach and intestines of mice at 20 days post-inoculation. Cultures of homogenates of the esophagus of most animals tested, and homogenates of the liver, lungs, spleen and kidneys of all animals tested, proved negative for C. albicans. Previous histological examinations of the GI tract of these colonized, non-immunocompromised mice showed hyphal elements associated with the stratified, squamous epithelium of the stomach in the region of the cardial-atrium fold. In this study, mice were immunocompromised by intraperitoneal injection of cyclophosphamide and cortisone acetate 11-14 days after oral-intragastric challenge with C. albicans and then sacrificed 20 days post-challenge. A high density of invasive hyphae was observed in the same, cardial-atrium region of the stomach of these animals. Cultures of the homogenized stomach showed a 100-fold increase in colony forming units (c.f.u.) of C. albicans compared with stomach homogenates of infected but non-immunocompromised controls. In addition, homogenates of the esophagus and selected body organs of most immunocompromised mice examined were positive for C. albicans by plate culture. When the immunocompromising drug treatment was delayed 3-5 weeks after oral-intragastric challenge, proliferation of C. albicans in the stomach and intestines was still evident, although fewer mice showed systemic spread and lower numbers of c.f.u. were recovered from body organ homogenates. Abscesses which contained both C. albicans hyphae and yeast cells were frequently observed in the liver and occasionally in the lungs and kidneys of immunocompromised mice sacrificed 20 days post-inoculation. The frequent occurrence of abscesses in the liver simulates a clinical variant of this mycosis, referred to as focal hepatic candidosis, which has been recognized with increasing frequency in immunocompromised patients. We suggest that the animal model described here may be particularly useful both for exploring methods which may prevent dissemination of C. albicans from localized foci of colonization in the GI tract after exposure of the host to immunocompromising drugs, and for testing the efficacy of anti-Candida drugs in clearance of the pathogen from body organs with established fungal abscesses.
用白色念珠菌对6日龄远交群Crl:CFW(SW)BR小鼠进行经口-胃内接种可导致胃肠道（GI）定植。我们已经表明，在没有免疫抑制治疗的情况下，接种后20天白色念珠菌主要定位于小鼠的胃和肠道。大多数受试动物食管匀浆以及所有受试动物的肝脏、肺、脾脏和肾脏匀浆的培养物，白色念珠菌检测均为阴性。之前对这些已定植、未免疫抑制小鼠胃肠道的组织学检查显示，在贲门-心房皱襞区域，菌丝成分与胃的复层鳞状上皮相关。在本研究中，在经口-胃内用白色念珠菌攻击11 - 14天后，通过腹腔注射环磷酰胺和醋酸可的松使小鼠免疫抑制，然后在攻击后20天处死。在这些动物胃的同一贲门-心房区域观察到高密度的侵袭性菌丝。与感染但未免疫抑制的对照小鼠的胃匀浆相比，匀浆化胃的培养物显示白色念珠菌的菌落形成单位（c.f.u.）增加了100倍。此外，通过平板培养，大多数免疫抑制小鼠的食管和选定身体器官的匀浆白色念珠菌检测呈阳性。当免疫抑制药物治疗在经口-胃内攻击后延迟3 - 5周时，白色念珠菌在胃和肠道中的增殖仍然明显，尽管较少的小鼠出现全身扩散，并且从身体器官匀浆中回收的c.f.u.数量较低。在接种后20天处死的免疫抑制小鼠的肝脏中经常观察到含有白色念珠菌菌丝和酵母细胞的脓肿，偶尔在肺和肾脏中也观察到。肝脏中脓肿的频繁出现模拟了这种真菌病的一种临床变体，称为局灶性肝念珠菌病，在免疫抑制患者中已越来越频繁地被认识到。我们认为，这里描述的动物模型可能特别有助于探索在宿主暴露于免疫抑制药物后，防止白色念珠菌从胃肠道局部定植灶扩散的方法，以及测试抗念珠菌药物清除已形成真菌脓肿的身体器官中病原体的疗效。
