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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 levels during primary RSV infection determine disease severity after reinfection.(a) Lung sections obtained from mice treated as in Fig 4, stained with periodic acid-Schiff (PAS) to observe mucus (bright purple; indicated by black arrowheads). Upper images taken at 100X with inset (black box) magnified underneath to 400X. (b) Quantification of airway mucus in mice treated as in a (methods). *P < 0.05 vs. indicated group (one-way ANOVA with Bonferroni post-hoc tests). Data are representative of two independent experiments (means ± s.e.m).
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ppat.1005217.g005: IL-33 levels during primary RSV infection determine disease severity after reinfection.(a) Lung sections obtained from mice treated as in Fig 4, stained with periodic acid-Schiff (PAS) to observe mucus (bright purple; indicated by black arrowheads). Upper images taken at 100X with inset (black box) magnified underneath to 400X. (b) Quantification of airway mucus in mice treated as in a (methods). *P < 0.05 vs. indicated group (one-way ANOVA with Bonferroni post-hoc tests). Data are representative of two independent experiments (means ± s.e.m).

Mentions: Lung sections were stained with periodic acid-Schiff (PAS) to visualize mucus-producing cells in the airways. Airway mucus production was significantly decreased in α-IL-33+NRR mice compared to controls, while mucus was significantly increased in rIL-33+ARR mice compared to controls (Fig 5a and 5b).


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 levels during primary RSV infection determine disease severity after reinfection.(a) Lung sections obtained from mice treated as in Fig 4, stained with periodic acid-Schiff (PAS) to observe mucus (bright purple; indicated by black arrowheads). Upper images taken at 100X with inset (black box) magnified underneath to 400X. (b) Quantification of airway mucus in mice treated as in a (methods). *P < 0.05 vs. indicated group (one-way ANOVA with Bonferroni post-hoc tests). Data are representative of two independent experiments (means ± s.e.m).
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005217.g005: IL-33 levels during primary RSV infection determine disease severity after reinfection.(a) Lung sections obtained from mice treated as in Fig 4, stained with periodic acid-Schiff (PAS) to observe mucus (bright purple; indicated by black arrowheads). Upper images taken at 100X with inset (black box) magnified underneath to 400X. (b) Quantification of airway mucus in mice treated as in a (methods). *P < 0.05 vs. indicated group (one-way ANOVA with Bonferroni post-hoc tests). Data are representative of two independent experiments (means ± s.e.m).
Mentions: Lung sections were stained with periodic acid-Schiff (PAS) to visualize mucus-producing cells in the airways. Airway mucus production was significantly decreased in α-IL-33+NRR mice compared to controls, while mucus was significantly increased in rIL-33+ARR mice compared to controls (Fig 5a and 5b).

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