Interleukin-22 regulates antimicrobial peptide expression and keratinocyte differentiation to control Staphylococcus aureus colonization of the nasal mucosa
Open accessAbstract
The local immune response occurring during Staphylococcus aureus nasal colonization remains ill-defined. Studies have highlighted the importance of T-cell immunity in controlling S. aureus colonization of the nasal mucosa. We extend these observations, identifying a critical role for interleukin (IL)-22 in this process. IL-22 is basally expressed within the nasal mucosa and is induced upon S. aureus colonization. IL-22 is produced by CD4+ and CD8+ T lymphocytes at this site, with innate-like lymphocytes also contributing. IL-22 −/− mice demonstrate significantly elevated levels of S. aureus nasal colonization as compared with wild-type (WT) mice. This was associated with reduced expression of antimicrobial peptides (AMPs) in the nose. Furthermore, expression of staphylococcal ligands loricrin and cytokeratin 10 was higher in the noses of IL-22 −/− as compared with WT mice. IL-17 has been shown to regulate S. aureus nasal colonization by controlling local neutrophil responses; however, IL-17 expression and neutrophil responses were comparable in the noses of IL-22 −/− and WT mice during S. aureus colonization. We conclude that IL-22 has an important role in controlling S. aureus nasal colonization through distinct mechanisms, with IL-22 mediating its effect exclusively by inducing AMP expression and controlling availability of staphylococcal ligands.
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IL-22-stimulated keratinocytes secrete increased amounts of defensins and other antimicrobial peptides that limit S. aureus proliferation.
“IL-22 stimulated keratinocytes, for example, secrete increased amounts of defensins and other antimicrobial peptides that limit S. aureus proliferation (Cho et al., 2010;Mulcahy et al., 2016).”
From Iron in infection and immunity (2020) · cites this paper as Mulcahy et al., 2016
The Results (section 'IL-22 does not regulate the IL-17 axis or neutrophil recruitment during nasal colonization'; page unavailable) report that nasal expression of defensins and other antimicrobial peptides was nearly abolished in IL-22-deficient mice. The Discussion reports that IL-22 enhances antimicrobial-peptide production in human keratinocytes and that these peptides can act against S. aureus. The paper does not show that IL-22-stimulated keratinocytes secrete increased amounts of those peptides or directly measure the claimed effect of that secretion on bacterial proliferation. (LLM, conf=0.85)
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- Authors
- Mulcahy, M. E., Leech, J. M., Renauld, J.-C., Mills, K. H., & McLoughlin, R. M.
- Affiliations
- Trinity College Dublin (IE)
- Ludwig Cancer Research (BE)
- Corresponding author
- McLoughlin, R.M.
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 9
- Issue
- 6
- Pages
- 1429-1441
- ISSN
- 1933-0219 (ISSN-L)
- OpenAlex
- W2314674414
- Cited by
- 58
- References
- 51
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 2
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Digital Access to Libraries (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Science Foundation Ireland (12/IP/1532)
- Irish Research Council (GOIPD/2014/385)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- IL-22, Staphylococcus aureus, nasal carriage, antimicrobial peptides, keratinocyte differentiation, loricrin, cytokeratin 10, innate-like lymphocytes, IL-17, neutrophils, nasal mucosa
- MeSH terms
- Interleukin-22, Adenosine Monophosphate, Animals, Cell Differentiation, Disease Models, Animal, Interleukins, Nasal Mucosa, Staphylococcal Infections, Staphylococcus aureus, Keratinocytes, Gene Expression, T-Lymphocyte Subsets, Mice, Knockout, Antimicrobial Cationic Peptides, Mice
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