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

PLoS Pathogens

Sridhar Jaligama¹  Tamekia L. Jones¹  Stephania A. Cormier¹  Bindiya Bagga¹  Dahui You¹  Greg I. Lee¹  Bishwas Shrestha²  John P. DeVincenzo²  Jeffrey N. Harding²  Cynthia Rovnaghi²  David Siefker²  Jordy Saravia² 

[1] Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Memphis, Tennessee, United States of America;Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America

关键词: Neonates;    Infants;    Mouse models;    Cytokines;    Immune response;    Mucus;    Rhinovirus infection;    Respiratory infections;   

DOI  :  10.1371/journal.ppat.1005217

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY