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.
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.
Authors: Michelle L Hernandez; Margaret Herbst; John C Lay; Neil E Alexis; Willie June Brickey; Jenny P Y Ting; Haibo Zhou; David B Peden Journal: J Allergy Clin Immunol Date: 2012-07-04 Impact factor: 10.793
Authors: Juliana K Ariffin; Kaustav das Gupta; Ronan Kapetanovic; Abishek Iyer; Robert C Reid; David P Fairlie; Matthew J Sweet Journal: Antimicrob Agents Chemother Date: 2015-12-28 Impact factor: 5.191
Authors: Emma L Beckett; Richard L Stevens; Andrew G Jarnicki; Richard Y Kim; Irwan Hanish; Nicole G Hansbro; Andrew Deane; Simon Keely; Jay C Horvat; Ming Yang; Brian G Oliver; Nico van Rooijen; Mark D Inman; Roberto Adachi; Roy J Soberman; Sahar Hamadi; Peter A Wark; Paul S Foster; Philip M Hansbro Journal: J Allergy Clin Immunol Date: 2013-02-04 Impact factor: 10.793
Authors: M R Starkey; D H Nguyen; A T Essilfie; R Y Kim; L M Hatchwell; A M Collison; H Yagita; P S Foster; J C Horvat; J Mattes; P M Hansbro Journal: Mucosal Immunol Date: 2013-09-18 Impact factor: 7.313