AUTHOR=Sanches Marcelo D’Alessandre , Mimura Luiza A. N. , Oliveira Larissa R. C. , Ishikawa Larissa L. W. , Garces Hans G. , Bagagli Eduardo , Sartori Alexandrina , Kurokawa Cilmery Suemi , Fraga-Silva Thais F. C. 

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02968

DOI=10.3389/fmicb.2018.02968

ISSN=1664-302X

ABSTRACT=<p>The genus <italic>Candida</italic> includes commensal fungi that can cause local and systemic infections, frequently involving vital organs as the central nervous system (CNS). <italic>Candida</italic> spp. occupy the fourth place among infections that affect the CNS. Although the incidence of <italic>Candida albicans</italic> is decreasing among patients under immunosuppressive therapies, the incidence of non-<italic>albicans Candida</italic> is increasing. In this context, the objective of this work was to evaluate the ability of non-<italic>albicans Candida</italic> species to spread to the CNS of immunocompetent and immunosuppressed mice. Adult female C57BL/6 mice were treated with prednisolone, intravenously infected with <italic>Candida glabrata</italic>, <italic>Candida krusei</italic> and <italic>Candida parapsilosis</italic> yeasts and then evaluated at the 3rd and 14th days after infection. All <italic>Candida</italic> 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 <italic>C. krusei</italic> immunosuppressed mice compared with immunocompetent ones. Additionally, <italic>C. krusei</italic> was able to transform into pseudohypha inside microglia <italic>in vitro</italic> infected cells and also to induce elevated nitric oxide production. Altogether, these results indicate that <italic>C. glabrata</italic>, <italic>C. krusei</italic> and <italic>C. parapsilosis</italic> are able to disseminate to the CNS and promote local inflammation in both immunocompetent and immunosuppressed mice. <italic>C. krusei</italic> displayed a distinct behavior at the CNS triggering a local Th1 profile. The possible contribution of these non-<italic>albicans Candida</italic> species to other CNS pathologies as multiple sclerosis, Parkinson’s and Alzheimer’s diseases deserves further attention.</p>