Journal article
Epithelial immune activation and intracellular invasion by non-typeable Haemophilus influenzae
- Abstract:
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Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1β, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL-1β. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.0MB, Terms of use)
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- Publisher copy:
- 10.3389/fcimb.2023.1141798
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Cellular and Infection Microbiology More from this journal
- Volume:
- 13
- Article number:
- 1141798
- Publication date:
- 2023-04-24
- Acceptance date:
- 2023-04-04
- DOI:
- EISSN:
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2235-2988
- Language:
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English
- Keywords:
- Pubs id:
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1339038
- Local pid:
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pubs:1339038
- Deposit date:
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2023-04-26
- ARK identifier:
Terms of use
- Copyright holder:
- Brown et al.
- Copyright date:
- 2023
- Rights statement:
- Copyright © 2023 Brown, Morgan, Donachie, Horton, Pavord, Arancibia-Cárcamo and Hinks. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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