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

Saravia J, You D, Shrestha B, Jaligama S, Siefker D, Lee GI, Harding JN, Jones TL, Rovnaghi C, Bagga B, DeVincenzo JP, Cormier SA - PLoS Pathog. (2015)

Bottom Line: The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive.Additionally, elevated IL-33 and IL-13 were observed in nasal aspirates from infants hospitalized with RSV; these cytokines declined during convalescence.This study provides a mechanism involving IL-33 and ILC2s in RSV mediated human asthma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

IL-33 and IL-13 concentrations are elevated in nasal aspirates from infants hospitalized with RSV infection.(a) Concentrations of IL-33 and IL-13 in nasal aspirates taken from RSV-infected infants (n = 19) on the first day (d1) of clinical presentation to Le Bonheur Children’s Hospital and again four weeks later (d28). (b) Correlation of IL-33 and IL-13 concentrations for all patients with d1 samples (n = 81). Samples with cytokine concentrations below the LOD of the assay are replaced by a value equal to the LOD divided by the square root of 2, and denoted with a filled circle. *P < 0.05 (Sign test (a) or Kendall’s tau correlation (b)).
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ppat.1005217.g007: IL-33 and IL-13 concentrations are elevated in nasal aspirates from infants hospitalized with RSV infection.(a) Concentrations of IL-33 and IL-13 in nasal aspirates taken from RSV-infected infants (n = 19) on the first day (d1) of clinical presentation to Le Bonheur Children’s Hospital and again four weeks later (d28). (b) Correlation of IL-33 and IL-13 concentrations for all patients with d1 samples (n = 81). Samples with cytokine concentrations below the LOD of the assay are replaced by a value equal to the LOD divided by the square root of 2, and denoted with a filled circle. *P < 0.05 (Sign test (a) or Kendall’s tau correlation (b)).

Mentions: Nasal aspirates were obtained from RSV-infected human infants (n = 81) on their initial day of clinical presentation (d1) at Le Bonheur Children’s Hospital. A follow-up nasal aspirate sample was obtained from some patients (n = 19) four weeks later (d28). Cytokine concentrations were analyzed in cell and mucus-free supernatants (Fig 7). In the paired samples, IL-33 and IL-13 levels were significantly elevated in d1 aspirates compared to d28 (Fig 7a). For all d1 samples, IL-33 levels significantly correlated with IL-13 (Fig 7b).


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

Saravia J, You D, Shrestha B, Jaligama S, Siefker D, Lee GI, Harding JN, Jones TL, Rovnaghi C, Bagga B, DeVincenzo JP, Cormier SA - PLoS Pathog. (2015)

IL-33 and IL-13 concentrations are elevated in nasal aspirates from infants hospitalized with RSV infection.(a) Concentrations of IL-33 and IL-13 in nasal aspirates taken from RSV-infected infants (n = 19) on the first day (d1) of clinical presentation to Le Bonheur Children’s Hospital and again four weeks later (d28). (b) Correlation of IL-33 and IL-13 concentrations for all patients with d1 samples (n = 81). Samples with cytokine concentrations below the LOD of the assay are replaced by a value equal to the LOD divided by the square root of 2, and denoted with a filled circle. *P < 0.05 (Sign test (a) or Kendall’s tau correlation (b)).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608776&req=5

ppat.1005217.g007: IL-33 and IL-13 concentrations are elevated in nasal aspirates from infants hospitalized with RSV infection.(a) Concentrations of IL-33 and IL-13 in nasal aspirates taken from RSV-infected infants (n = 19) on the first day (d1) of clinical presentation to Le Bonheur Children’s Hospital and again four weeks later (d28). (b) Correlation of IL-33 and IL-13 concentrations for all patients with d1 samples (n = 81). Samples with cytokine concentrations below the LOD of the assay are replaced by a value equal to the LOD divided by the square root of 2, and denoted with a filled circle. *P < 0.05 (Sign test (a) or Kendall’s tau correlation (b)).
Mentions: Nasal aspirates were obtained from RSV-infected human infants (n = 81) on their initial day of clinical presentation (d1) at Le Bonheur Children’s Hospital. A follow-up nasal aspirate sample was obtained from some patients (n = 19) four weeks later (d28). Cytokine concentrations were analyzed in cell and mucus-free supernatants (Fig 7). In the paired samples, IL-33 and IL-13 levels were significantly elevated in d1 aspirates compared to d28 (Fig 7a). For all d1 samples, IL-33 levels significantly correlated with IL-13 (Fig 7b).

Bottom Line: The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive.Additionally, elevated IL-33 and IL-13 were observed in nasal aspirates from infants hospitalized with RSV; these cytokines declined during convalescence.This study provides a mechanism involving IL-33 and ILC2s in RSV mediated human asthma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus