Retinoic acid enhanced neutrophil antimicrobial functions including cathelicidin (LL-37) production against MRSA, and directly inhibited Group A Streptococcus growth, reducing skin lesion size and bacterial burden in a mouse infection model.
LL-37 production increasedRetinoic acid stimulated human neutrophils to produce the antimicrobial peptide cathelicidin (LL-37), enhancing their ability to kill drug-resistant bacteria
What the researchers found
Retinoic acid stimulated human neutrophils to produce LL-37 antimicrobial peptide, reactive oxygen species, and extracellular traps, enhancing MRSA killing in vitro. RA directly inhibited GAS growth and, in a murine skin infection model, topical RA reduced both skin lesion size and bacterial burden.
Why it matters
Antimicrobial resistance is a growing crisis, and this research suggests vitamin A derivatives could enhance the body's natural antimicrobial peptide defenses. The finding that retinoic acid boosts cathelicidin (LL-37) production — a key human antimicrobial peptide — while also directly killing certain bacteria opens a potential dual-action therapeutic approach for drug-resistant skin infections.
The numbers in context
RA boosted neutrophil killing of methicillin-resistant bacteria. Effects on antimicrobial peptide production were characterized.
How the study worked
In vitro experiments using primary human neutrophils treated with retinoic acid, tested against MRSA, E. coli K1, P. aeruginosa, and GAS. Antimicrobial peptide production (LL-37), ROS, and NETs were measured. In vivo murine skin infection models tested topical RA against both MRSA and GAS.
Who was studied
Human neutrophils and cutaneous bacterial pathogens
What this study cannot tell us
In vitro and animal study with no human clinical data. RA failed to reduce MRSA burden in vivo despite in vitro activity, suggesting the in vitro-to-in vivo translation is not straightforward. GAS-specific effects may not generalize to other pathogens. Murine skin immunity differs from human skin immunity.
How to read the evidence
Rated preliminary: in vitro and animal model data only, with no human clinical validation. The MRSA results did not translate from in vitro to in vivo.
When this study was published
Published in 2024. Represents current preclinical research on vitamin A and antimicrobial peptide interactions.
The bigger picture
This work connects vitamin A biology to antimicrobial peptide research, showing that retinoic acid can upregulate cathelicidin (LL-37) — one of the body's most important natural antibiotics. This could inform strategies for boosting innate immunity against antibiotic-resistant bacteria, particularly for skin and soft tissue infections.
Questions still open
- Could topical retinoic acid formulations be developed as adjunct therapy for drug-resistant skin infections in humans?
- Does systemic vitamin A status affect cathelicidin levels and susceptibility to skin infections?
- Why did retinoic acid directly inhibit GAS but not MRSA, E. coli, or Pseudomonas?
Common questions
Can vitamin A help fight antibiotic-resistant infections?
What is cathelicidin (LL-37) and why does it matter?
Read the original research
The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens.
Infectious microbes & diseases, 6(2), 65-73
Citation
Stream, Alexandra; Corriden, Ross; Döhrmann, Simon; Gallo, Richard L; Nizet, Victor; Anderson, Ericka L. (2024). The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens.. Infectious microbes & diseases, 6(2), 65-73. https://doi.org/10.1097/im9.0000000000000145