Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus

Jie Sun, Amber Cardani, Ashish K. Sharma, Victor E. Laubach, Robert S. Jack, Werner Müller, Thomas J. Braciale

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection.

Original languageEnglish (US)
Article numbere1002173
JournalPLoS Pathogens
Volume7
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

Fingerprint

Respiratory Syncytial Virus Infections
Interleukin-10
Pneumonia
T-Lymphocytes
Respiratory System
Interleukin-10 Receptors
Bronchiolitis
Respiratory Syncytial Viruses
Adaptive Immunity
Regulator Genes
Antiviral Agents
Cytokines
Inflammation
Lung

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus. / Sun, Jie; Cardani, Amber; Sharma, Ashish K.; Laubach, Victor E.; Jack, Robert S.; Müller, Werner; Braciale, Thomas J.

In: PLoS Pathogens, Vol. 7, No. 8, e1002173, 08.2011.

Research output: Contribution to journalArticle

Sun, Jie ; Cardani, Amber ; Sharma, Ashish K. ; Laubach, Victor E. ; Jack, Robert S. ; Müller, Werner ; Braciale, Thomas J. / Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus. In: PLoS Pathogens. 2011 ; Vol. 7, No. 8.
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