Strain-dependent effects of Nontypeable Haemophilus influenzae (NTHi) on human macrophage function

Abstract

Nontypeable Haemophilus influenzae (NTHi) is a heterogeneous respiratory tract pathogen implicated in opportunistic infections and exacerbations of chronic respiratory diseases, such as COPD and asthma. In these diseases, airway macrophages have impaired phagocytic ability, contributing to chronic airway colonisation by NTHi. It is unclear whether macrophage responses to NTHi are strain-dependent, highlighting a possible mechanism by which certain NTHi strains can persist within the airway. The aim of this work was to characterise macrophage responses following infection with different clinical strains of NTHi. Monocyte-derived macrophages (MDM) isolated from blood of healthy volunteers were infected with NTHi ST14 or ST201 for 6h, incubated with antibiotics for a further 18h, followed by inflammatory pathway analysis by PCR or ELISA. Measurement of NTHi hel gene expression demonstrated increased presence of ST14, compared to ST201 in MDM at 24h (p This work suggests that ST14 is more persistent in MDM than ST201, resulting in increased expression of inflammatory markers. These data indicate that MDM respond differently to different NTHi strains. Investigating these strain differences will increase our understanding of the role of NTHi in exacerbations of chronic respiratory disease.