Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33

Jordy Saravia, Dahui You, Bishwas Shrestha, Sridhar Jaligama, David Siefker, Greg I. Lee, Jeffrey N. Harding, Tamekia Jones, Cynthia Rovnaghi, Bindiya Bagga, John Devincenzo, Stephania Cormier

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) is the most common cause of infant hospitalizations and severe RSV infections are a significant risk factor for childhood asthma. The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive. Using an age-appropriate mouse model of RSV, we show that IL-33 plays a critical role in the immunopathogenesis of severe RSV, which is associated with higher group 2 innate lymphoid cells (ILC2s) specifically in neonates. Infection with RSV induced rapid IL-33 expression and an increase in ILC2 numbers in the lungs of neonatal mice; this was not observed in adult mice. Blocking IL-33 with antibodies or using an IL-33 receptor knockout mouse during infection was sufficient to inhibit RSV immunopathogenesis (i.e., airway hyperresponsiveness, Th2 inflammation, eosinophilia, and mucus hyperproduction); whereas administration of IL-33 to adult mice during RSV infection was sufficient to induce RSV disease. Additionally, elevated IL-33 and IL-13 were observed in nasal aspirates from infants hospitalized with RSV; these cytokines declined during convalescence. In summary, IL-33 is necessary, either directly or indirectly, to induce ILC2s and the Th2 biased immunopathophysiology observed following neonatal RSV infection. This study provides a mechanism involving IL-33 and ILC2s in RSV mediated human asthma.

Original languageEnglish (US)
Article numbere1005217
JournalPLoS Pathogens
Volume11
Issue number10
DOIs
StatePublished - Jan 1 2015

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Respiratory Syncytial Viruses
Virus Diseases
Respiratory Syncytial Virus Infections
Asthma
Human respiratory syncytial virus
Interleukin-13
Interleukin-33
Eosinophilia
Mucus
Nose
Knockout Mice
Hospitalization
Newborn Infant
Lymphocytes
Cytokines
Inflammation
Lung
Antibodies
Infection

All Science Journal Classification (ASJC) codes

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

Cite this

Saravia, J., You, D., Shrestha, B., Jaligama, S., Siefker, D., Lee, G. I., ... Cormier, S. (2015). Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33. PLoS Pathogens, 11(10), [e1005217]. https://doi.org/10.1371/journal.ppat.1005217

Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33. / Saravia, Jordy; You, Dahui; Shrestha, Bishwas; Jaligama, Sridhar; Siefker, David; Lee, Greg I.; Harding, Jeffrey N.; Jones, Tamekia; Rovnaghi, Cynthia; Bagga, Bindiya; Devincenzo, John; Cormier, Stephania.

In: PLoS Pathogens, Vol. 11, No. 10, e1005217, 01.01.2015.

Research output: Contribution to journalArticle

Saravia, J, You, D, Shrestha, B, Jaligama, S, Siefker, D, Lee, GI, Harding, JN, Jones, T, Rovnaghi, C, Bagga, B, Devincenzo, J & Cormier, S 2015, 'Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33', PLoS Pathogens, vol. 11, no. 10, e1005217. https://doi.org/10.1371/journal.ppat.1005217
Saravia J, You D, Shrestha B, Jaligama S, Siefker D, Lee GI et al. Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33. PLoS Pathogens. 2015 Jan 1;11(10). e1005217. https://doi.org/10.1371/journal.ppat.1005217
Saravia, Jordy ; You, Dahui ; Shrestha, Bishwas ; Jaligama, Sridhar ; Siefker, David ; Lee, Greg I. ; Harding, Jeffrey N. ; Jones, Tamekia ; Rovnaghi, Cynthia ; Bagga, Bindiya ; Devincenzo, John ; Cormier, Stephania. / Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33. In: PLoS Pathogens. 2015 ; Vol. 11, No. 10.
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