Development of Mucosal Candida Colonization and Dissemination Model in Immunodeficient Mice

Candida albican is one of common commensals but can become opportunistic pathogen in susceptible hosts. As the similar symptoms to bacterial infection, the Candida infection is difficult to diagnose and causes >40% of mortality in patients due to the delays in antifungal therapy. To investigate the biomarker or therapeutic drugs for systemic Candida infection, we used immunodeficient RAG mice to mimic immune compromised humans. After gastrointestinal infection, a dose-dependent survival was seen in RAG mice with the 100% of survival in 10⁶ and 10⁵ and 0% in 10⁷ of Candida albican strain SC5314 infection. In contrast, none of wild-type C57BL/6 mice died in Candida infection. In 10⁷ Candida infected RAG mice, colonization of Candida albican was detected in stool with the fungal burden of 10^2-3 cfu/ml from day 5-14 and all mice died between day 12-19 due to the disseminated Candida infection. The serological and cellular changes were screened for the surrogate biomarkers represented the transition of Candida albican colonization to systemic dissemination. The significant increase of IL-6 and galectin-3 found in day 9-12 after Candida infection suggested these two molecules have potential as the biomarkers for the life-threaten systemic Candida infection.