Establishment Of Nontypeable Haemophilus Influenzae Airway Infection Murine Model

Nontypeable Haemophilus influenzae (NTHi) is reported to be colonised more in the lower airways of COPD and asthma patients. The colonization is known to be associated with considerable airway inflammation and cause increased frequency of exacerbations as well as lung cancer. Treatment of respiratory tract infection with NTHi is often only partially successful with ongoing infection and inflammation. Successful treatment will be dependent on a better understanding of the pathogenesis and pharmacological response to this bacterium although there is no or little NTHi airway infection model reported. Therefore, aim of this study is to establish NTHi airway infection model in mice. NTHi (ATCC49766) at sub-lethal concentration was administered intranasally to intact or immunocompromised (IC) A/J mice, pre-treated with hydrocortisone and cyclophosphamide. BALF and lung were collected a day after bacteria intranasal inoculation, and the bacterial burden and biomarkers were evaluated. The IC mice showed more than 50-fold higher bacteria burden in BALF (geometric mean 3.6 Log, CFU/mL in intact mice vs 5.4 Log, CFU/mL in IC mice) and lung (4.5 Log, CFU/g in intact mice vs 6.4 Log, CFU/g in IC mice), and showed much higher levels of biomarkers CXCL1 and malonaldehyde in BALF. Levofloxacin, when dosed intranasally or orally, inhibited bacterial burden completely. Thus, we were able to establish NTHi airway infection model, which can be used to understand pathogenesis/host response to NTHi and to identify new therapy for NTHi airway infection.