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- Title
Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza.
- Authors
Liu, Francesca Diane M.; Kenngott, Elisabeth E.; Schröter, Micha F.; Kühl, Anja; Jennrich, Silke; Watzlawick, Ralf; Hoffmann, Ute; Wolff, Thorsten; Norley, Stephen; Scheffold, Alexander; Stumhofer, Jason S.; Saris, Christiaan J. M.; Schwab, Jan M.; Hunter, Christopher A.; Debes, Gudrun F.; Hamann, Alf
- Abstract
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.
- Subjects
INTERLEUKIN-27; INFLUENZA viruses; INFLAMMATION; CYTOKINES; IMMUNOPATHOLOGY
- Publication
PLoS Pathogens, 2014, Vol 10, Issue 5, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1004110