Adiponectin inhibits eosinophil recruitment and is protective in invasive aspergillosis

Abstract

Abstract Aspergillus fumigatus is a fungal pathogen associated with allergy, asthma, and invasive infection in susceptible individuals. Our previous results suggested that eosinophils may be a novel therapeutic target in invasive aspergillosis (IA) patients that do not respond to conventional pharmacotherapy. Eosinophil recruitment is induced by inhalation of the fungal cell wall polysaccharide chitin. However, the mechanisms of immune regulation that drive this recruitment are not well understood. We observed decreased levels of the metabolic-regulating cytokine adiponectin in the lungs and serum of mice after chitin aspiration, suggesting that adiponectin may be involved in the regulation of type 2 lung immune responses. Co-aspiration of adiponectin with chitin significantly reduced eosinophil accumulation in the lungs, and airway eosinophil recruitment in adiponectin-deficient mice was increased with chitin aspiration. In addition, chitin aspiration resulted in decreased surface expression of the adiponectin receptor AdipoR1 on eosinophils. Most significantly, airway accumulation of eosinophils, disease severity, and fungal burden were increased in adiponectin knockout mice with IA. This may be due to a direct inhibition of eosinophil recruitment, as recombinant adiponectin inhibited chemotaxis of bone marrow-derived eosinophils in vitro. These results suggest that adiponectin inhibits potentially detrimental lung eosinophil recruitment in response to chitin-containing pathogens. Increased understanding of the relationship between metabolic and immune regulation may ultimately result in novel therapies for obesity and allergic and infectious disease.