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Combined Haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma
  1. Ama-Tawiah Essilfie1,
  2. Jodie L Simpson1,2,
  3. Margaret L Dunkley3,
  4. Lucy C Morgan4,
  5. Brian G Oliver5,
  6. Peter G Gibson1,2,
  7. Paul S Foster1,
  8. Philip M Hansbro1
  1. 1Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia
  2. 2Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, New South Wales, Australia
  3. 3Hunter Immunology Ltd, Newcastle, New South Wales, Australia
  4. 4Department of Thoracic Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia
  5. 5Sydney Medical School and Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia
  1. Correspondence to Professor Philip Hansbro, Infection and Immunity, The David Maddison Clinical Sciences Building, University of Newcastle, Cnr King and Watt Sts, Newcastle, NSW 2300, Australia; philip.hansbro{at}


Background 20–30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often have chronic airway bacterial colonisation and Haemophilus influenzae is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear.

Objectives To investigate the relationship between H influenzae respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease.

Methods BALB/c mice were intratracheally infected with H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12–15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21).

Results The combination of H influenzae infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited.

Conclusions The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.

  • Chronic infection
  • Haemophilus influenzae
  • neutrophilic asthma
  • steroid resistance
  • innate immune dysfunction
  • Th17
  • asthma
  • bacterial infection
  • innate immunity
  • cytokine biology
  • eosinophil biology
  • exhaled airway markers
  • neutrophil biology
  • airway epithelium
  • bronchiectasis
  • complementary medicine
  • cystic fibrosis
  • lung cancer
  • non-small cell lung cancer
  • paediatric lung disaese
  • rare lung diseases
  • tobacco and the lung
  • asthma pharmacology
  • COPD exacerbations
  • COPD pathology
  • COPD pharmacology
  • macrophage biology
  • respiratory infection
  • asthma guidelines
  • asthma mechanisms
  • cough/mechanisms/pharmacology
  • COPD mechanisms
  • allergic lung disease
  • paediatric asthma
  • pneumonia
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  • Funding Hunter Medical Research Institute, the National Health and Medical Research Council of Australia, The Australian Research Council, and University of Newcastle.

  • Competing interests None.

  • Ethics approval All experiments were approved by the Animal Care and Ethics Committee, University of Newcastle.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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