Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments
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Significance Paneth cells provide intestinal host defense against pathogens and control the healthy microbiota by secreting antimicrobial peptides. We show that the most abundant secreted Paneth cell products, human defensin HD-5 and HD-6, show a distinct susceptibility to proteolytic digestion by human duodenal fluid. While HD-5 is digested in many fragments, HD-6 is stable and still able to form nanonets. The occurring fragments of HD-5 were antimicrobially active against microorganisms. We provide proof of concept about microbiome modulating capacities in vivo, which includes an increase of Akkermansia sp. Our results indicate that fragmentation of defensins increases antimicrobial diversity and further adds to the complexity of host microbial interaction at interfaces. Fragmentation could lead to new antimicrobial peptides with possible therapeutic usage.
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Intestinal antimicrobial peptides exhibit manifold interactions with the microbiota and are an essential component in shaping its configuration.
“Intestinal AMPs exhibit manifold interactions with the microbiota and are an essential component in shaping its configuration.49”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [49]
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- Authors
- Ehmann, D., Wendler, J., Koeninger, L., Larsen, I. S., Klag, T., Berger, J., Marette, A., Schaller, M., Stange, E. F., Malek, N. P., Jensen, B. A. H., & Wehkamp, J.
- Affiliations
- Universitätsklinikum Tübingen (DE)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Max Planck Institute for Developmental Biology (DE)
- University of Copenhagen (DK)
- Corresponding author
- Wehkamp, J.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-02-11
- Volume
- 116
- Issue
- 9
- Pages
- 3746-3751
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6397583
- OpenAlex
- W2914417447
- Cited by
- 112
- References
- 46
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 20 · 2020: 15 · 2019: 5
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (238358106)
- European Research Council (DEFENSINSACTIVITY_310842)
- Lundbeckfonden (R232-2016-2425)
- Novo Nordisk Foundation (NNF17OC0026698)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Paneth cells, antimicrobial peptides, proteolytic digestion, duodenal fluid, peptide fragmentation, nanonets, Akkermansia, gut microbiota, host-microbe interactions, antimicrobial activity
- MeSH terms
- Host Microbial Interactions, Animals, Anti-Infective Agents, Humans, Hydrogen-Ion Concentration, Intestinal Mucosa, Oxidation-Reduction, Peptides, Paneth Cells, alpha-Defensins, Mice, Proteolysis, Cellular Microenvironment, Microbiota
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