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

Strain-dependent effects of Nontypeable Haemophilus influenzae (NTHi) on human macrophage function
Strain-dependent effects of Nontypeable Haemophilus influenzae (NTHi) on human macrophage function
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<0.05). MDM expression of IFNß, TLR4 and TLR7 was not significantly different between strains. However, MDM expression of CXCL10, RIG-I and NFκB was induced significantly more by ST14 (p<0.05). In contrast, levels of CXCL10 released into MDM supernatants did not differ between the two strains. However, MDM production of IL1ß, IL6 and IL8 was higher in response to ST14 infection compared to ST201 (p<0.05).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
bacteria, infection, asthma, macrophage
2312-0541
Ackland, Jodie
dba59510-7535-47f8-b2ba-2d49dfa7fbd8
Cleary, David
f4079c6d-d54b-4108-b346-b0069035bec0
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Wilkinson, Tom
8c55ebbb-e547-445c-95a1-c8bed02dd652
Staples, Karl
e0e9d80f-0aed-435f-bd75-0c8818491fee
Ackland, Jodie
dba59510-7535-47f8-b2ba-2d49dfa7fbd8
Cleary, David
f4079c6d-d54b-4108-b346-b0069035bec0
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Wilkinson, Tom
8c55ebbb-e547-445c-95a1-c8bed02dd652
Staples, Karl
e0e9d80f-0aed-435f-bd75-0c8818491fee

Ackland, Jodie, Cleary, David, Christodoulides, Myron, Wilkinson, Tom and Staples, Karl (2019) Strain-dependent effects of Nontypeable Haemophilus influenzae (NTHi) on human macrophage function. ERJ Open Research, 5 (Suppl 2), [PP135]. (doi:10.1183/23120541.lungscienceconference-2019.pp135).

Record type: Meeting abstract

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<0.05). MDM expression of IFNß, TLR4 and TLR7 was not significantly different between strains. However, MDM expression of CXCL10, RIG-I and NFκB was induced significantly more by ST14 (p<0.05). In contrast, levels of CXCL10 released into MDM supernatants did not differ between the two strains. However, MDM production of IL1ß, IL6 and IL8 was higher in response to ST14 infection compared to ST201 (p<0.05).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

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More information

Published date: 7 March 2019
Keywords: bacteria, infection, asthma, macrophage

Identifiers

Local EPrints ID: 441601
URI: http://eprints.soton.ac.uk/id/eprint/441601
ISSN: 2312-0541
PURE UUID: 53653dd7-9b44-4f09-870e-9609df5a0233
ORCID for Jodie Ackland: ORCID iD orcid.org/0000-0003-3120-3620
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

Catalogue record

Date deposited: 19 Jun 2020 16:30
Last modified: 07 Oct 2021 02:03

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