Progranulin aggravates pulmonary immunopathology during influenza virus infection.

Abstract

Progranulin (PGRN) exerts multiple functions in various inflammatory diseases. However, the role of PGRN in the pathogenesis of virus infection is unknown. Here, we demonstrated that PGRN production was up-regulated in clinical and experimental influenza, which contributed to the deleterious inflammatory response after influenza virus infection in mice. PGRN-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced influx of neutrophils and monocytes/macrophages, release of cytokines and chemokines, and permeability of the alveolar-epithelial barrier without affecting viral clearance. Our findings suggest that PGRN exacerbates pulmonary immunopathology during influenza virus infection.