IL-27 Negatively Controls Antifungal Activity in a Model of Invasive Pulmonary Aspergillosis

Abstract

Invasive pulmonary aspergillosis is a life-threatening disease, particularly in immunocompromised patients despite currently available therapy. Interleukin-27 (IL-27) is an important regulatory cytokine in infection and immunity. However, its role in the pathogenesis of invasive pulmonary aspergillosis remains unknown. Here we found that A. fumigatus pulmonary infection induced an elevated production of IL-27 in the lung. As compared to wild-type (WT) mice, IL-27 receptor (IL-27R)-deficient mice developed less severe infection when challenged with A. fumigatus conidia, as evidenced by the decreased fungal colonization and pathology of lungs and the increased survival. IL-27R deficiency led to significantly higher production of IFN-γ in the lung after A. fumigatus infection, and the increased resistance to invasive pulmonary A.fumigatus infection in IL-27R-deficient mice was ablated by neutralizing IFN-γ. Importantly, neutralization of IL-27 could protect WT mice against invasive pulmonary A.fumigatus infection. Our data therefore suggests an important role of IL-27 in impairing anti-A.fumigatus host immunity, which may have translational implications in treating clinical cases of invasive pulmonary aspergillosis.