Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma?
Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2022-09-01
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| Series: | European Respiratory Review |
| Online Access: | http://err.ersjournals.com/content/31/165/220008.full |
| _version_ | 1811264434014781440 |
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| author | Mary Ashley Brown Maisha Jabeen Gurpreet Bharj Timothy S.C. Hinks |
| author_facet | Mary Ashley Brown Maisha Jabeen Gurpreet Bharj Timothy S.C. Hinks |
| author_sort | Mary Ashley Brown |
| collection | DOAJ |
| description | Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research. |
| first_indexed | 2024-04-12T20:04:15Z |
| format | Article |
| id | doaj.art-1df355f88f204efd84aa53b3184529f7 |
| institution | Directory Open Access Journal |
| issn | 0905-9180 1600-0617 |
| language | English |
| last_indexed | 2024-04-12T20:04:15Z |
| publishDate | 2022-09-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | European Respiratory Review |
| spelling | doaj.art-1df355f88f204efd84aa53b3184529f72022-12-22T03:18:27ZengEuropean Respiratory SocietyEuropean Respiratory Review0905-91801600-06172022-09-013116510.1183/16000617.0008-20220008-2022Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma?Mary Ashley Brown0Maisha Jabeen1Gurpreet Bharj2Timothy S.C. Hinks3 Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Experimental Medicine Division, Nuffield Dept of Medicine, University of Oxford, Oxford, UK Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Experimental Medicine Division, Nuffield Dept of Medicine, University of Oxford, Oxford, UK Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Experimental Medicine Division, Nuffield Dept of Medicine, University of Oxford, Oxford, UK Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Experimental Medicine Division, Nuffield Dept of Medicine, University of Oxford, Oxford, UK Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research.http://err.ersjournals.com/content/31/165/220008.full |
| spellingShingle | Mary Ashley Brown Maisha Jabeen Gurpreet Bharj Timothy S.C. Hinks Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? European Respiratory Review |
| title | Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? |
| title_full | Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? |
| title_fullStr | Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? |
| title_full_unstemmed | Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? |
| title_short | Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? |
| title_sort | non typeable haemophilus influenzae airways infection the next treatable trait in asthma |
| url | http://err.ersjournals.com/content/31/165/220008.full |
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