Macrophage inflammatory responses to Non-typeable Haemophilus influenzae (NTHi) are strain-dependent

Abstract

The airway macrophage is crucial for immune surveillance and pathogen clearance, however, this function is impaired in chronic respiratory diseases such as COPD and asthma. This may lead to colonization of the airways by Nontypeable Haemophilus influenzae (NTHi). NTHi is a heterogeneous organism and this heterogeneity could result in strain-dependent differences in macrophage responses, leading to airway persistence of certain NTHi strains. The aim of this work was to investigate macrophage responses to different clinical strains of NTHi.

Strain diversity assessment of eight NTHi clinical isolates was performed using ParSNP. Subsequently, three strains (ST14, 201 and 408) were chosen to infect monocyte-derived macrophages (MDM) isolated from the blood of healthy volunteers to investigate expression of inflammatory pathways by PCR or ELISA. Measurement of NTHi hel gene expression revealed increased presence of ST14 and ST408 compared to ST201 (p<0.05). MDM expression of IFN-β and RIG-I was significantly higher for ST14 compared to ST408 (p<0.05), but not ST201. In contrast, expression of CXCL10, RIG-I and NFκB was significantly higher for ST14 compared to ST201 (p<0.05) but not ST408. MDM expression of TLR4 and TLR7 did not differ between strains. There were also no significant differences in cytokine production between ST408 and ST14, however ST14 induced higher release of IL-1β, IL-6 and IL-8 from MDM compared to ST201 (p<0.05).

This work suggests ST14 elicits a differential MDM inflammatory response compared to ST201 and ST408. These differences highlight that NTHi heterogeneity must be further explored in order to comprehend the role of NTHi in chronic respiratory disease.