The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them
Abstract
:1. The Ambivalent Role of the Skin Microbiota in Wound Healing
2. Certain Members of the Skin Microbiota Can Have a Negative Impact on Wound Healing
3. Positive Effect of Some Commensals and Probiotics on Wound Healing
4. Adrenergic Receptors (ARs) Are Expressed in Many Cells of the Skin and Contribute to Wound Healing
4.1. Keratinocytes
4.2. Immune Cells
4.3. Fibroblasts
4.4. Blood Vessels
5. Interplay between Adrenaline and Skin Bacteria
5.1. TA-Producing Skin Microbiota Might Accelerate Wound Healing via ARs
5.2. Adrenaline Controls Not Only Sympathetic Nervous System but Also Quorum Sensing in Bacteria
6. Topical Probiotics Are a Therapeutic Option in the Treatment of Chronic Wounds
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ARs | adrenergic receptors |
ß2-ARs | beta-2-adrenergic-receptors |
cAMP | cyclic-adenosine monophosphate |
DOP | dopamine |
EPI | epinephrine (adrenaline) |
ERK | extracellular signal-regulated kinase |
FGF2 | fibroblast growth factor 2 |
KGF1 | keratinocyte growth factor 1 |
PKA | protein kinase A |
PEA | phenethylamine |
PP2A | phosphatase 2A |
sadA | gene encoding staphylococcal aromatic amino acid decarboxylase |
SadA | enzyme of staphylococcal aromatic amino acid decarboxylase |
SNS | sympathetic nervous system |
TAs | trace amines (PEA, TRY, TYM) |
TRY | tryptamine |
TYM | tyramine |
VEGF-A | vascular endothelial growth factor A |
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Species | Effector | Mode of Action | References |
---|---|---|---|
(A) Adverse effect on wound healing | |||
Peptostreptococcus spp. (P. magnus, P. vaginalis, and P. asaccharolyticus) | Bacterial supernatant | Inhibit fibroblast proliferation, keratinocyte proliferation and repopulation, and endothelial tubule formation | [17] |
Staphylococcus aureus, Pseudomonas aeruginosa, Peptoniphilus sp., Stenotrophomonas sp., Finegoldia sp., Serratia sp., Bacillus sp., Enterococcus sp., Enterobacter aerogenes, Acinetobacter baumanii, Klebsiella pneumoniae, Proteus mirabilis, Aspergillus fumigatus, Enterobacter cloacae, Corynebacterium frankenforstense, Corynebacterium striatum, Alcaligenes faecalis and Acinetobacter sp. | Biofilm | Related to wound chronicity | [12,13,39,40] |
Skin commensals | Can be particulate cell wall peptidoglycan | Augment S. aureus pathogenesis | [41] |
Bacteria | Muramyl dipeptide | Delay wound repair by reducing re-epithelialization; increasing inflammation; and upregulating of murine β-defensins 1, 3, and 14 | [42] |
Pathogenic staphylococci | Secreted factors | Activate the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT signaling pathways and suppress NF-κB activation | [28] |
Pathogenic fungi | Wound necrosis | [43] | |
(B) Promoting effect on wound healing | |||
Staphylococcus epidermidis and possibly other skin commensals with sadA gene | Trace amines | Accelerate wound healing by partially antagonizing the β-adrenergic receptor | [19,44] |
Skin commensals predominantly from Staphylococcus | Bacteriocins | Inhibit pathogenic Gram-positive bacteria such as Cutibacterium acnes, Staphylococcus epidermidis, and MRSA | [45] |
Staphylococcus caprae and other coagulase-negative staphylococci | Autoinducing peptide | Inhibit quorum sensing of S. aureus | [31,46] |
Lactobacilli | Organic acids | Antimicrobial activity against skin pathogens and prevent biofilm formation | [37,47,48] |
Lactobacillus rhamnosus, Lactobacillus reuteri | Lysate | Increase keratinocyte proliferation and migration | [49] |
S. epidermidis | Short chain fatty acids | Suppress the growth of S. aureus and C. acnes | [50] |
S. epidermidis | Delta-toxin (PSMγ) | Cooperates with the host-derived antimicrobial peptides in the innate immune system to eliminate pathogens | [51] |
S. epidermidis | Induces IL-17A+ CD8+ T cells, enhances innate barrier immunity, and limits pathogen invasion | [9] | |
S. epidermidis and S. hominis | Antimicrobial peptides | Selectively kill S. aureus and synergize with the human AMP LL-37 | [36] |
Commensal staphylococci | Secreted factors | Induce expression of the AMPs HBD-3 and RNase7 in primary human keratinocytes via Toll-like receptor (TLR)-2, EGFR, and NF-κB activation | [28] |
Commensal staphylococci | Lipoteichoic acid | Inhibit both inflammatory cytokine release from keratinocytes and inflammation triggered by injury through a TLR2-dependent mechanism | [52] |
S. aureus | Peptidoglycan | Ameliorate cyclophosphamide-impaired wound healing | [53] |
Staphylococci | Surface proteins SpA and Sbi | Initiate signaling cascades that lead to the early recruitment of neutrophils, modulate their lifespan in the skin milieu, and contribute to proper abscess formation and bacterial eradication | [30] |
Skin commensals | Trigger activation of neutrophils to express the chemokine CXCL10 to kill exposed microbiota; activate pDC to produce type I IFNs, which accelerate wound closure by triggering skin inflammation and early T-cell-independent wound repair responses | [29] | |
Skin commensals | Induce T-cell responses that lead to protection from pathogens and accelerated skin wound closure | [54] |
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Luqman, A.; Götz, F. The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them. Int. J. Mol. Sci. 2021, 22, 4996. https://doi.org/10.3390/ijms22094996
Luqman A, Götz F. The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them. International Journal of Molecular Sciences. 2021; 22(9):4996. https://doi.org/10.3390/ijms22094996
Chicago/Turabian StyleLuqman, Arif, and Friedrich Götz. 2021. "The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them" International Journal of Molecular Sciences 22, no. 9: 4996. https://doi.org/10.3390/ijms22094996