Gastrointestinal and systemic candidosis in immunocompromised mice

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.