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PPARγ controls Dectin-1 expression required for host antifungal defense against Candida albicans

Amandine Galès1, Annabelle Conduché, José Bernad

  • 1UMR-MD3 EA2405 Université de Toulouse III; UPS; Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, PMRNP2I, Toulouse, France.

Plos Pathogens
|January 12, 2010
PubMed

Insights

Peroxisome proliferator activated receptor gamma (PPARgamma) ligands control fungal infections by regulating Dectin-1 in macrophages. This finding suggests PPARgamma ligands may treat candidiasis in immunocompromised patients.

Area of Science:

  • Immunology
  • Microbiology
  • Pharmacology

Background:

  • Interleukin-13 (IL-13) and peroxisome proliferator activated receptor gamma (PPARgamma) ligands were previously shown to reduce Candida albicans colonization.
  • Dectin-1 plays a critical role in macrophage-mediated immune responses against fungal pathogens.

Purpose of the Study:

  • To investigate the role of Dectin-1 in controlling fungal gastrointestinal infections mediated by PPARgamma ligands.
  • To elucidate the mechanisms by which PPARgamma ligands and IL-13 influence macrophage antifungal activity.

Main Methods:

  • Utilized a macrophage-specific Dectin-1 deficient mice model.
  • Assessed phagocytosis and reactive oxygen intermediate production in macrophages.
  • Investigated the involvement of Mannose Receptor in fungal recognition.
  • Examined the signaling pathway linking IL-13, Dectin-1, and PPARgamma.

Main Results:

  • Dectin-1 is essential for controlling fungal gastrointestinal infections when using PPARgamma ligands.
  • Impaired phagocytosis and reactive oxygen intermediate release were observed in Dectin-1 deficient macrophages treated with PPARgamma ligands or IL-13.
  • Mannose Receptor is involved in recognizing non-opsonized Candida albicans by macrophages.
  • IL-13 modulation of Dectin-1 expression is dependent on the PPARgamma signaling pathway.

Conclusions:

  • PPARgamma plays a crucial role in the alternative activation of macrophages by Th2 cytokines like IL-13.
  • PPARgamma ligands show therapeutic potential for treating esophageal and gastrointestinal candidiasis, particularly in immunocompromised individuals and those with metabolic diseases.

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