PPARγ controls Dectin-1 expression required for host antifungal defense against Candida albicans.
PLoS Pathog
; 6(1): e1000714, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-20062524
ABSTRACT
We recently showed that IL-13 or peroxisome proliferator activated receptor gamma (PPARgamma) ligands attenuate Candida albicans colonization of the gastrointestinal tract. Here, using a macrophage-specific Dectin-1 deficient mice model, we demonstrate that Dectin-1 is essential to control fungal gastrointestinal infection by PPARgamma ligands. We also show that the phagocytosis of yeast and the release of reactive oxygen intermediates in response to Candida albicans challenge are impaired in macrophages from Dectin-1 deficient mice treated with PPARgamma ligands or IL-13. Although the Mannose Receptor is not sufficient to trigger antifungal functions during the alternative activation of macrophages, our data establish the involvement of the Mannose Receptor in the initial recognition of non-opsonized Candida albicans by macrophages. We also demonstrate for the first time that the modulation of Dectin-1 expression by IL-13 involves the PPARgamma signaling pathway. These findings are consistent with a crucial role for PPARgamma in the alternative activation of macrophages by Th2 cytokines. Altogether these data suggest that PPARgamma ligands may be of therapeutic value in esophageal and gastrointestinal candidiasis in patients severely immunocompromised or with metabolic diseases in whom the prevalence of candidiasis is considerable.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Candidíase
/
Transdução de Sinais
/
PPAR gama
/
Macrófagos
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Proteínas de Membrana
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article