PPARγ Controls Dectin-1 Expression Required for Host Antifungal Defense against Candida albicans

PLoS Pathogens

José Bernad¹  Marie-Denise Linas¹  David Olagnier²  Agnès Coste²  Annabelle Conduché³  Guillaume Martin-Blondel³  Johan Auwerx⁴  Lise Lefevre⁴  Maryse Béraud⁵  Bernard Pipy⁵  Amandine Galès⁵ 

[1] Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, PMRNP2I, Toulouse, France;RH2PT Université de la Méditerranée - Ministère de la Défense, Marseille, France;UPS;UMR-MD3;UMR-MD3 EA2405 Université de Toulouse III

关键词: Macrophages;    C;    ida albicans;    Phagocytosis;    Antifungals;    Yeast infections;    Gastrointestinal infections;    Respiratory burst;    Small interfering RNAs;   

DOI  :  10.1371/journal.ppat.1000714

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

We recently showed that IL-13 or peroxisome proliferator activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ 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 PPARγ signaling pathway. These findings are consistent with a crucial role for PPARγ in the alternative activation of macrophages by Th2 cytokines. Altogether these data suggest that PPARγ 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.

【 授权许可】

CC BY