Timed action of IL-27 protects from immunopathology while preserving defense in influenza.

• Main Authors: Francesca Diane M Liu, Elisabeth E Kenngott, Micha F Schröter, Anja Kühl, Silke Jennrich, Ralf Watzlawick, Ute Hoffmann, Thorsten Wolff, Stephen Norley, Alexander Scheffold, Jason S Stumhofer, Christiaan J M Saris, Jan M Schwab, Christopher A Hunter, Gudrun F Debes, Alf Hamann
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-05-01
• Series: PLoS Pathogens
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24809349/?tool=EBI

Infection with influenza virus can result in massive pulmonary infiltration and potentially fatal immunopathology. Understanding the endogenous mechanisms that control immunopathology could provide a key to novel adjunct therapies for this disease. Here we show that the cytokine IL-27 plays a crucial role in protection from exaggerated inflammation during influenza virus infection. Using Il-27ra-/- mice, IL-27 was found to limit immunopathology, neutrophil accumulation, and dampened TH1 or TH17 responses via IL-10-dependent and -independent pathways. Accordingly, the absence of IL-27 signals resulted in a more severe disease course and in diminished survival without impacting viral loads. Consistent with the delayed expression of endogenous Il-27p28 during influenza, systemic treatment with recombinant IL-27 starting at the peak of virus load resulted in a major amelioration of lung pathology, strongly reduced leukocyte infiltration and improved survival without affecting viral clearance. In contrast, early application of IL-27 impaired virus clearance and worsened disease. These findings demonstrate the importance of IL-27 for the physiological control of immunopathology and the potential value of well-timed IL-27 application to treat life-threatening inflammation during lung infection.