Adiponectin pathway activation dampens inflammation and enhances alveolar macrophage fungal killing via LC3-associated phagocytosis.
Sri Harshini GoliJoo-Yeon LimNese Basaran-AkgulSteven Paul TempletonPublished in: bioRxiv : the preprint server for biology (2024)
Although innate immunity is critical for antifungal host defense against the human opportunistic fungal pathogen Aspergillus fumigatus, potentially damaging inflammation must be controlled. Adiponectin (APN) is an adipokine produced mainly in adipose tissue that exerts anti-inflammatory effects in adipose-distal tissues such as the lung. We observed 100% mortality and increased fungal burden and inflammation in neutropenic mice with invasive aspergillosis (IA) that lack APN or the APN receptors AdipoR1 or AdipoR2. Alveolar macrophages (AMs), early immune sentinels that detect and respond to lung infection, express both receptors, and APN-/- AMs exhibited an inflammatory/M1 phenotype that was associated with decreased fungal killing. Pharmacological stimulation of AMs with AdipoR agonist AdipoRon partially rescued deficient killing in APN-/- AMs that was dependent on both receptors. Finally, APN-enhanced fungal killing was associated with increased activation of the non-canonical LC3 pathway of autophagy. Thus, our study identifies a novel role for APN in LC3-mediated killing of A.fumigatus.
Keyphrases
- oxidative stress
- adipose tissue
- insulin resistance
- simultaneous determination
- metabolic syndrome
- endothelial cells
- candida albicans
- mass spectrometry
- gene expression
- signaling pathway
- cell death
- high fat diet
- liquid chromatography
- endoplasmic reticulum stress
- minimally invasive
- dna methylation
- cardiovascular events
- cardiovascular disease
- induced pluripotent stem cells
- skeletal muscle
- high resolution mass spectrometry
- wild type