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J Infect Dis ; 209(5): 799-810, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24096333

RESUMO

BACKGROUND: The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive. METHODS AND RESULTS: We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-γKO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN-γ-dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN-γ and iNKT cells. CONCLUSIONS: Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN-γ produced, in part, by iNKT cells.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Coinfecção/imunologia , Glicolipídeos/imunologia , Interferon gama/imunologia , Células T Matadoras Naturais/imunologia , Animais , Bactérias/imunologia , Medula Óssea/imunologia , Medula Óssea/microbiologia , Medula Óssea/virologia , Candidíase/microbiologia , Candidíase/virologia , Coinfecção/microbiologia , Coinfecção/virologia , Interleucina-6/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células T Matadoras Naturais/microbiologia , Células T Matadoras Naturais/virologia , Neutropenia/imunologia , Neutropenia/microbiologia , Neutropenia/virologia
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