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NTHi-IAV coinfection of macrophages alters infection outcomes and inflammatory responses

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.


2312-0541
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
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), 76. (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.


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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
ORCID for Jodie Ackland: ORCID iD orcid.org/0000-0003-3120-3620
ORCID for Ashley Heinson: ORCID iD orcid.org/0000-0001-8695-6203
ORCID for David Cleary: ORCID iD orcid.org/0000-0003-4533-0700
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731
ORCID for Karl Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 10 Oct 2022 16:49
Last modified: 31 Jan 2023 03:04

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Contributors

Author: Jodie Ackland ORCID iD
Author: Ashley Heinson ORCID iD
Author: David Cleary ORCID iD
Author: Tom M.A. Wilkinson
Author: Karl Staples ORCID iD

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