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TLR2-mediated innate immune priming boosts lung anti-viral immunity
- Source :
- European Respiratory Journal. 58:2001584
- Publication Year :
- 2020
- Publisher :
- European Respiratory Society (ERS), 2020.
-
Abstract
- BackgroundWe assessed whether Toll-like receptor (TLR)2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III interferon (IFN) production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show,in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7 days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1 day before infection increased expression of 190 lung tissue immune genes. This tissue gene expression signature was absent with INNA-X treatment 7 days before infection, suggesting an alternate mechanism, potentiallyviaestablishment of immune cell-mediated mucosal innate immunity.In vitro, INNA-X treatment induced a priming response defined by upregulated IFN-λ, chemokine and anti-microbial gene expression that preceded an accelerated response to infection enriched for nuclear factor (NF)-κB-regulated genes and reduced viral loads, even in epithelial cells derived from asthmatic donors with intrinsic delayed anti-viral immune response.ConclusionAirway epithelial cell TLR2 activation induces prolonged innate immune priming, defined by early NF-κB activation, IFN-λ expression and lymphocyte recruitment. This response enhanced anti-viral innate immunity and reduced virus-induced airway inflammation.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Chemokine
medicine.medical_treatment
Lymphocyte
Antiviral Agents
Fas ligand
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Immunity
medicine
Animals
Humans
Lung
Innate immune system
biology
business.industry
Epithelial Cells
Immunity, Innate
Toll-Like Receptor 2
TLR2
030104 developmental biology
Cytokine
medicine.anatomical_structure
030220 oncology & carcinogenesis
Immunology
biology.protein
business
Subjects
Details
- ISSN :
- 13993003 and 09031936
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- European Respiratory Journal
- Accession number :
- edsair.doi.dedup.....4d101f054bccc18da811a67ca829ce1d