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The genus  Candida  includes commensal fungi that can cause local and systemic infections, frequently involving vital organs as the central nervous system (CNS).  Candida  spp. occupy the fourth place among infections that affect the CNS. Although the incidence of  Candida albicans  is decreasing among patients under immunosuppressive therapies, the incidence of non- albicans Candida  is increasing. In this context, the objective of this work was to evaluate the ability of non- albicans Candida  species to spread to the CNS of immunocompetent and immunosuppressed mice. Adult female C57BL/6 mice were treated with prednisolone, intravenously infected with  Candida glabrata ,  Candida krusei  and  Candida parapsilosis  yeasts and then evaluated at the 3rd and 14th days after infection. All  Candida  species disseminated to the brain from immunocompetent animals and induced local inflammation at the third day post-infection. The immunosuppression resulted in body weight loss, leukopenia and reduced IL-2 production by spleen cell cultures. Higher fungal loads were recovered from the CNS of immunosuppressed mice. Inflammatory infiltration associated to a Th1 subset profile was higher in brain samples from  C. krusei  immunosuppressed mice compared with immunocompetent ones. Additionally,  C. krusei  was able to transform into pseudohypha inside microglia  in vitro  infected cells and also to induce elevated nitric oxide production. Altogether, these results indicate that  C. glabrata ,  C. krusei  and  C. parapsilosis  are able to disseminate to the CNS and promote local inflammation in both immunocompetent and immunosuppressed mice.  C. krusei  displayed a distinct behavior at the CNS triggering a local Th1 profile. The possible contribution of these non- albicans Candida  species to other CNS pathologies as multiple sclerosis, Parkinson’s and Alzheimer’s diseases deserves further attention.

Differential Behavior of Non-albicans Candida Species in the Central Nervous System of Immunocompetent and Immunosuppressed Mice