Timed action of IL-27 protects from immunopathology while preserving defense in influenza.
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 crucia...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2014
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/f46c7abf103043808e7e70a88af3992e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:f46c7abf103043808e7e70a88af3992e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:f46c7abf103043808e7e70a88af3992e2021-11-18T06:06:36ZTimed action of IL-27 protects from immunopathology while preserving defense in influenza.1553-73661553-737410.1371/journal.ppat.1004110https://doaj.org/article/f46c7abf103043808e7e70a88af3992e2014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24809349/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Infection 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.Francesca Diane M LiuElisabeth E KenngottMicha F SchröterAnja KühlSilke JennrichRalf WatzlawickUte HoffmannThorsten WolffStephen NorleyAlexander ScheffoldJason S StumhoferChristiaan J M SarisJan M SchwabChristopher A HunterGudrun F DebesAlf HamannPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 5, p e1004110 (2014) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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 Timed action of IL-27 protects from immunopathology while preserving defense in influenza. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Francesca Diane M Liu |
| title |
Timed action of IL-27 protects from immunopathology while preserving defense in influenza. |
| title_short |
Timed action of IL-27 protects from immunopathology while preserving defense in influenza. |
| title_full |
Timed action of IL-27 protects from immunopathology while preserving defense in influenza. |
| title_fullStr |
Timed action of IL-27 protects from immunopathology while preserving defense in influenza. |
| title_full_unstemmed |
Timed action of IL-27 protects from immunopathology while preserving defense in influenza. |
| title_sort |
timed action of il-27 protects from immunopathology while preserving defense in influenza. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/f46c7abf103043808e7e70a88af3992e |
| work_keys_str_mv |
AT francescadianemliu timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT elisabethekenngott timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT michafschroter timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT anjakuhl timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT silkejennrich timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT ralfwatzlawick timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT utehoffmann timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT thorstenwolff timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT stephennorley timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT alexanderscheffold timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT jasonsstumhofer timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT christiaanjmsaris timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT janmschwab timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT christopherahunter timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT gudrunfdebes timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza AT alfhamann timedactionofil27protectsfromimmunopathologywhilepreservingdefenseininfluenza |
| _version_ |
1718424577933049856 |