Recombinant human β-defensin 2 delivery improves smoking-induced lung neutrophilia and bacterial exacerbation

Research output: Contribution to journalJournal articleResearchpeer-review


  • Fulltext

    Accepted author manuscript, 1.73 MB, PDF document

  • Nadia Milad
  • Marie Pineault
  • Gabrielle Bouffard
  • Michaël Maranda-Robitaille
  • Ariane Lechasseur
  • Marie Josée Beaulieu
  • Sophie Aubin
  • Jensen, Benjamin Anderschou Holbech
  • Mathieu C. Morissette

Treatment of the cigarette smoke-associated lung diseases, such as chronic obstructive pulmonary disease (COPD), has largely focused on broad-spectrum anti-inflammatory therapies. However, these therapies, such as high-dose inhaled corticosteroids, enhance patient susceptibility to lung infection and exacerbation. Our objective was to assess whether the cationic host defense peptide, human β-defensin 2 (hBD-2), can simultaneously reduce pulmonary inflammation in cigarette smoke-exposed mice while maintaining immune competence during bacterial exacerbation. Mice were exposed to cigarette smoke acutely (4 days) or chronically (5 days/wk for 7 wk) and administered hBD-2 intranasally or by gavage. In a separate model of acute exacerbation, chronically exposed mice treated with hBD-2 were infected with nontypeable Haemophilus influenzae before euthanasia. In the acute exposure model, cigarette smoke-associated pulmonary neutrophilia was significantly blunted by both local and systemic hBD-2 administration. Similarly, chronically exposed mice administered hBD-2 therapeutically exhibited reduced pulmonary neutrophil infiltration and downregulated proinflammatory signaling in the lungs compared with vehicle-treated mice. Finally, in a model of acute bacterial exacerbation, hBD-2 administration effectively limited neutrophil infiltration in the lungs while markedly reducing pulmonary bacterial load. This study shows that hBD-2 treatment can significantly attenuate lung neutrophilia induced by cigarette smoke exposure while preserving immune competence and promoting an appropriate host-defense response to bacterial stimuli.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1
Pages (from-to)L37-L47
Number of pages11
Publication statusPublished - 2022

    Research areas

  • antimicrobial peptides, bacteria, cigarette smoke, inflammation, lung

ID: 314440477