Translocation model of Candida albicans in DBA-2/J mice with protein calorie malnutrition mimics hematogenous candidiasis in humans.

To elucidate the mechanism of translocation of Candida albicans from the intestine to the bloodstream, we attempted to establish a murine model for hematogenous translocation of C. albicans using DBA-2/J mice with protein calorie malnutrition (PCM). PCM severely affected the development of the intestinal epithelia; thereby, the keratin and mucinous layers became very thin. Oral inoculation with C. albicans resulted in long-term colonization in the intestine of the PCM mice but not the well-nourished animals. Chemotherapy with a combination of cyclophosphamide and methotrexate, which started four days after oral inoculation of C. albicans, resulted in the systemic dissemination of C. albicans from the intestine in the PCM mice. Among systemic organs, C. albicans was first isolated from the liver, in which focal necrosis, containing fungal balls of yeast-like forms and/or hyphae, was formed. Subsequently, C. albicans was first recovered from the blood of the infected PCM mice at one day after the isolation from the liver, and thereafter, candidemia continued to increase its intensity until death. Histological study indicated that C. albicans gained entry into the systemic organs from the epithelia of the esophago-cardiac junction as well as the Ileo-cecal portions of the infected mice. The results of our present study therefore suggest that this PCM mouse model may be useful for better understanding of the chemotherapy-induced translocation by C. albicans from the gut to the systemic organs in compromised humans.