NTHi-IAV coinfection of macrophages alters infection outcomes and inflammatory responses
NTHi-IAV coinfection of macrophages alters infection outcomes and inflammatory responses
Nontypeable Haemophilus influenzae (NTHi) chronically colonises the airway of individuals with chronic respiratory disease, with persistence suggested to be facilitated by invasion of airway macrophages. Previous data supports an interaction between NTHi colonisation and the risk of viruses exacerbating underlying respiratory diseases. As exacerbations are the main cause of morbidity and mortality of respiratory diseases, the drivers of this increased risk need to be identified.
The aim of this work was to investigate whether prior NTHi infection compromises the ability of macrophages to respond to a subsequent viral challenge. A monocyte-derived macrophage (MDM)-NTHi intracellular persistence model was adapted to include coinfection with the influenza A virus (IAV). Compared to pathogen-alone controls, NTHi presence significantly increased by 190% (p<0.05), whereas the percentage of IAV-infected MDM significantly decreased (23.9% to 6.8%, p<0.01) during co-infection. This decreased viral infection was associated with NTHi-mediated transcriptomic upregulation of MDM antiviral responses (FDR p<0.05) and IFN-β release (p<0.05) prior to IAV challenge. Coinfected MDM released higher levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-8, IL-15, IL-23 and IL-36β, all p<0.05) compared to IAV infection alone.
This work demonstrates that although prior NTHi infection primed MDM to better respond to IAV infection, coinfection resulted in increased NTHi load and MDM pro-inflammatory responses. Considering the interactions of colonising airway bacteria and viral infections on host immune responses may better inform on treatment strategies to reduce exacerbations.
76
Ackland, Jodie
dba59510-7535-47f8-b2ba-2d49dfa7fbd8
Heinson, Ashley
822775d1-9379-4bde-99c3-3c031c3100fb
Cleary, David
f4079c6d-d54b-4108-b346-b0069035bec0
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Wilkinson, Tom M.A.
9c51b529-00ce-45d2-b6e0-b623f61fdf82
Staples, Karl
e0e9d80f-0aed-435f-bd75-0c8818491fee
9 May 2022
Ackland, Jodie
dba59510-7535-47f8-b2ba-2d49dfa7fbd8
Heinson, Ashley
822775d1-9379-4bde-99c3-3c031c3100fb
Cleary, David
f4079c6d-d54b-4108-b346-b0069035bec0
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Wilkinson, Tom M.A.
9c51b529-00ce-45d2-b6e0-b623f61fdf82
Staples, Karl
e0e9d80f-0aed-435f-bd75-0c8818491fee
Ackland, Jodie, Heinson, Ashley, Cleary, David, Christodoulides, Myron, Wilkinson, Tom M.A. and Staples, Karl
(2022)
NTHi-IAV coinfection of macrophages alters infection outcomes and inflammatory responses.
ERJ Open Research, 8 (8), .
(doi:10.1183/23120541.LSC-2022.76).
Record type:
Meeting abstract
Abstract
Nontypeable Haemophilus influenzae (NTHi) chronically colonises the airway of individuals with chronic respiratory disease, with persistence suggested to be facilitated by invasion of airway macrophages. Previous data supports an interaction between NTHi colonisation and the risk of viruses exacerbating underlying respiratory diseases. As exacerbations are the main cause of morbidity and mortality of respiratory diseases, the drivers of this increased risk need to be identified.
The aim of this work was to investigate whether prior NTHi infection compromises the ability of macrophages to respond to a subsequent viral challenge. A monocyte-derived macrophage (MDM)-NTHi intracellular persistence model was adapted to include coinfection with the influenza A virus (IAV). Compared to pathogen-alone controls, NTHi presence significantly increased by 190% (p<0.05), whereas the percentage of IAV-infected MDM significantly decreased (23.9% to 6.8%, p<0.01) during co-infection. This decreased viral infection was associated with NTHi-mediated transcriptomic upregulation of MDM antiviral responses (FDR p<0.05) and IFN-β release (p<0.05) prior to IAV challenge. Coinfected MDM released higher levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-8, IL-15, IL-23 and IL-36β, all p<0.05) compared to IAV infection alone.
This work demonstrates that although prior NTHi infection primed MDM to better respond to IAV infection, coinfection resulted in increased NTHi load and MDM pro-inflammatory responses. Considering the interactions of colonising airway bacteria and viral infections on host immune responses may better inform on treatment strategies to reduce exacerbations.
This record has no associated files available for download.
More information
e-pub ahead of print date: 9 May 2022
Published date: 9 May 2022
Identifiers
Local EPrints ID: 470410
URI: http://eprints.soton.ac.uk/id/eprint/470410
ISSN: 2312-0541
PURE UUID: b7d4bbc4-96df-4af8-83ce-9b2f8211c8df
Catalogue record
Date deposited: 10 Oct 2022 16:49
Last modified: 19 Apr 2024 01:59
Export record
Altmetrics
Contributors
Author:
Ashley Heinson
Author:
Tom M.A. Wilkinson
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics