Asthma development is associated with low mucosal IL-10 during viral infections in early life

Allergy. 2024 Nov;79(11):2981-2992. doi: 10.1111/all.16276. Epub 2024 Sep 2.

Abstract

Background: Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting.

Objectives: To investigate in situ virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma.

Methods: We included 493 episodes of acute respiratory illnesses in 277 children aged 0-3 years from the COPSAC2010 mother-child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high-sensitivity MesoScale Discovery kits and compared between children with and without viral PCR-identification in nasopharyngeal samples. Finally, we investigated whether the virus-specific immune response was associated with asthma by age 6 years.

Results: Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-ɣ, TNF-α, CCL4, CXCL10 and IL-10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL-10 (FDR <0.05) during viral episodes compared to children not developing asthma.

Conclusion: We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL-10) immune mediator level. This provides insight into the interplay between early-life viral infections, airway immunity and asthma development.

Keywords: asthma; cytokines; infant; preschool child; respiratory tract infections; viruses.

MeSH terms

  • Asthma* / etiology
  • Asthma* / immunology
  • Asthma* / virology
  • Biomarkers
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-10* / metabolism
  • Male
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / virology
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / virology
  • Virus Diseases* / immunology

Substances

  • Interleukin-10
  • Cytokines
  • Biomarkers