Mucosal Immunol. 2026 Feb 9:S1933-0219(26)00012-7. doi: 10.1016/j.mucimm.2026.01.012. Online ahead of print.
ABSTRACT
RATIONALE: Bronchiolitis is the commonest cause of hospital admission in children under the age of 1 year, most cases being due to respiratory syncytial virus (RSV) infection. The mechanisms causing infantile bronchiolitis are incompletely understood but include a deficient mucosal interferon response, neutrophilic inflammation and enhanced mucosal Type-2 responses.
OBJECTIVES: We sought to determine the mucosal immune processes associated with severe paediatric bronchiolitis.
METHODS: We performed transcriptomic analyses on mucosal samples from infants hospitalized with Moderate (n = 48) and Severe (n = 40) bronchiolitis. Differential expression and regression analyses determined genes associated with different severity categories. Responses were modelled in vitro using air-liquid interface human nasal epithelial cell culture models.
MEASUREMENTS AND MAIN RESULTS: We confirmed weakened interferon-associated signalling in severe RSV and non-RSV bronchiolitis but unexpectedly found elevated IL-36α (an IL-1 family cytokine implicated in chronic inflammatory diseases) early in infection. Conversely, IL36A was decreased in whole blood during severe RSV, suggesting that this association is unique to the mucosa. In human nasal epithelial cells grown in vitro under air-liquid interface we found IL-36α to be produced by epithelial cells during RSV infection and that its secretion is enhanced by neutrophils.
CONCLUSIONS: These findings implicate mucosal IL-36α as a dominant feature of severe paediatric bronchiolitis.
ONE SENTENCE SUMMARY: Mucosal transcriptomics identifies IL-36 secretion as a feature of life-threatening paediatric RSV and all-cause bronchiolitis associated with interferon response failure.
PMID:41672198 | DOI:10.1016/j.mucimm.2026.01.012