Cutaneous Injury Induces the Release of Cathelicidin Anti-Microbial Peptides Active Against Group A Streptococcus
Open accessAbstract
Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. The human and mouse cathelicidins (LL-37 and CRAMP, respectively) are expressed at select epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these peptides play a part in the protection of skin against wound infections, the anti-microbial activity of LL-37 and CRAMP was determined against the common wound pathogen group A Streptococcus, and their expression was examined after cutaneous injury. We observed a large increase in the expression of cathelicidins in human and murine skin after sterile incision, or in mouse following infection by group A Streptococcus. The appearance of cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition from granulocyctes that migrate to the site of injury. Synthesis and deposition in the wound was accompanied by processing from the inactive prostorage form to the mature C-terminal peptide. Analysis of anti-microbial activity of this C-terminal peptide against group A Streptococcus revealed that both LL-37 and CRAMP potently inhibited bacterial growth. Action against group A Streptococcus occurred in conditions that typically abolish the activity of anti-microbial peptides against other organisms. Thus, cathelicidins are well suited to provide defense against infections due to group A Streptococcus, and represent an important element of cutaneous innate immunity.
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Early events in the innate immune response to skin injury include the recruitment of neutrophils and the induction of antimicrobial peptides, particularly cathelicidin LL-37 in humans.
“Early events in the innate immune response to skin injury include the recruitment of neutrophils and the induction of antimicrobial peptides, particularly, in humans, the cathelicidin LL-37.17”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [17]
Suction blister wounds, where the blister roof is still intact, do not show substantial inflammation, whereas excisional wounds, ultraviolet-induced skin damage, superficial tape stripping or chemical skin irritants, and contact sensitizers cause inflammatory infiltrates.
“Interestingly, suction blister wounds, where the blister roof is still intact, do not show substantial inflammation,9 whereas excisional wounds, ultraviolet (UV)-induced skin damage, superficial tape stripping or chemical skin irritants, and contact sensitizers cause inflammatory infiltrates,17,23–26”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [17]
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Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons
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Self-citationThe human cathelicidin LL-37 — A pore-forming antibacterial peptide and host-cell modulator
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In vitro and In vivo Wound Healing-Promoting Activities of Human Cathelicidin LL-37
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Cytokine Milieu of Atopic Dermatitis Skin Subverts the Innate Immune Response to Vaccinia Virus
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Self-citationCathelicidins: a family of endogenous antimicrobial peptides
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Postsecretory Processing Generates Multiple Cathelicidins for Enhanced Topical Antimicrobial Defense
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Interleukin-17A and Keratinocytes in Psoriasis
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The molecular pathology of rosacea
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“Early events in the innate immune response to skin injury include the recruitment of neutrophils and the induction of antimicrobial peptides, particularly, in humans, the cathelicidin LL-37.(17) Neutrophils are recruited by a series of asparagine–leucine– arginine (ELR) motif-containing CXC chemokines that are secrete…”
BackgroundInfluentialBiology and clinical relevance of naturally occurring antimicrobial peptides
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Self-citationSelective Killing of Vaccinia Virus by LL-37: Implications for Eczema Vaccinatum
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Self-citationCathelicidin Anti-Microbial Peptide Expression in Sweat, an Innate Defense System for the Skin
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Self-citationAntimicrobial Peptide Resistance Mechanisms of Human Bacterial Pathogens
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Antimicrobial peptides: natural effectors of the innate immune system
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Self-citationCathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity
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Immunomodulatory Properties of Defensins and Cathelicidins
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Cutaneous Defense Mechanisms by Antimicrobial Peptides
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Self-citationAntimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence
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Vitamin D Induces the Antimicrobial Protein hCAP18 in Human Skin
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Antimicrobial skin peptides and proteins
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Anti-Fungal Activity of Cathelicidins and their Potential Role in Candida albicans Skin Infection
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Self-citationHost defense peptides and their antimicrobial-immunomodulatory duality
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Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease
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Self-citationImmunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection
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Cathelicidins, essential gene-encoded mammalian antibiotics
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Cathelicidin Antimicrobial Peptides are Expressed in Salivary Glands and Saliva
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Self-citation
- Authors
- Dorschner, R. A., Pestonjamasp, V. K., Tamakuwala, S., Ohtake, T., Rudisill, J., Nizet, V., Agerberth, B., Gudmundsson, G. H., & Gallo, R. L.
- Affiliations
- University of California San Diego (US)
- Karolinska Institutet (SE)
- Corresponding author
- Gallo, Richard L.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 117
- Issue
- 1
- Pages
- 91-97
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2085793178
- Cited by
- 567
- References
- 56
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 17 · 2022: 11 · 2021: 12 · 2020: 16 · 2019: 25 · 2018: 23 · 2017: 24 · 2016: 20 · 2015: 26 · 2014: 25 · 2013: 23 · 2012: 33
- FWCI
- 14.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI48176, R21AI048176)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-44379)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- cathelicidin, LL-37, cramps, Streptococcus pyogenes, skin wounds, wound infection, antimicrobial peptides, innate immunity, keratinocytes, granulocytes, skin
- MeSH terms
- Amino Acid Sequence, Animals, Female, Humans, Male, Mice, Inbred C57BL, Molecular Sequence Data, Proteins, RNA, Messenger, Skin, Streptococcal Infections, Streptococcus pyogenes, Wound Healing, Keratinocytes, Gene Expression, Antimicrobial Cationic Peptides, Mice, Cathelicidins
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