Format

Send to

Choose Destination
PLoS Pathog. 2014 May 8;10(5):e1004110. doi: 10.1371/journal.ppat.1004110. eCollection 2014 May.

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

Author information

1
Deutsches Rheuma-Forschungszentrum and Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, United States of America.
2
Deutsches Rheuma-Forschungszentrum and Charité-Universitätsmedizin Berlin, Berlin, Germany.
3
Research Center ImmunoSciences (RCIS), Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, United States of America.
5
Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
6
Robert Koch-Institut, Berlin, Germany.
7
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
8
Department of Inflammation Research, Amgen Inc., Thousand Oaks, California, United States of America.

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.

PMID:
24809349
PMCID:
PMC4014457
DOI:
10.1371/journal.ppat.1004110
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center