Abstract
Rationale Non-typeable Haemophilus influenzae (NTHi) is a common inhabitant of the human nasopharynx and upper airways that can cause opportunistic infections of the airway mucosa including bronchopulmonary infections in patients with chronic obstructive pulmonary disease (COPD). It is clear that opportunistic infections contribute significantly to inflammatory exacerbations of COPD; however, there remains much to be learned regarding specific host and microbial determinants of persistence and/or clearance in this context.
Methods In this study, we used a recently described ferret model for COPD, in which animals undergo chronic long-term exposure to cigarette smoke, to define host–pathogen interactions during COPD-related NTHi infections.
Results NTHi bacteria colonised the lungs of smoke-exposed animals to a greater extent than controls, and elicited acute host inflammation and neutrophilic influx and activation, along with a significant increase in airway resistance and a decrease in inspiratory capacity consistent with inflammatory exacerbation; notably, these findings were not observed in air-exposed control animals. NTHi bacteria persisted within multicellular biofilm communities within the airway lumen, as evidenced by immunofluorescent detection of bacterial aggregates encased within a sialylated matrix as is typical of NTHi biofilms and differential bacterial gene expression consistent with the biofilm mode of growth.
Conclusions Based on these results, we conclude that acute infection with NTHi initiates inflammatory exacerbation of COPD disease. The data also support the widely held hypothesis that NTHi bacteria persist within multicellular biofilm communities in the lungs of patients with COPD.
Abstract
Infection of smoke-exposed ferrets with COPD results in mucus obstruction and respiratory symptoms as in patients, and the bacteria are in a distinct mode of growth consistent with biofilms https://bit.ly/3euXpbQ
Footnotes
Author contributions: B.C. Hunt, A. Gaggar, S.M. Rowe, S.V. Raju and W.E. Swords conceived and designed the experiments. B.C. Hunt, S. Stanford, X. Xu and J. Li performed the experiments. B.C. Hunt, A. Gaggar, S.V. Raju and W.E. Swords analysed and interpreted the data. B.C. Hunt and W.E. Swords wrote the manuscript.
This article has supplementary material available from openres.ersjournals.com
Conflict of interest: B.C. Hunt has nothing to disclose.
Conflict of interest: D. Stanford has nothing to disclose.
Conflict of interest: X. Xu has nothing to disclose.
Conflict of interest: J. Li has nothing to disclose.
Conflict of interest: A. Gaggar has nothing to disclose.
Conflict of interest: S.M. Rowe reports grants, personal fees and nonfinancial support from Synedgen/Synspira during the conduct of the study; grants and personal fees from Novartis, grants and personal fees from Bayer, grants from Translate Bio, nonfinancial support from Proteostasis, grants, personal fees and nonfinancial support from Galapagos/Abbvie, grants, personal fees and other from Synedgen/Synspira, grants from Eloxx, grants from Celtaxsys, grants, personal fees, nonfinancial support and other from Vertex Pharmaceuticals Inc., personal fees from Renovion, grants and personal fees from Arrowhead, grants and other from Ionis, grants from AstraZeneca, outside the submitted work.
Conflict of interest: S.V. Raju has nothing to disclose.
Conflict of interest: W.E. Swords reports grants from Merck outside the submitted work.
- Received April 19, 2020.
- Accepted May 18, 2020.
- Copyright ©ERS 2020
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.