Scientists have demonstrated for the first time how Staphylococcus aureus—a leading cause of skin infections—reshapes the immune system’s inflammatory responses in children with a rare skin condition.
Findings from the research could in the not-too-distant future inform efforts to predict patient-specific outcomes because the study highlighted a connection between different strains of S. aureus and disease severity, data in the study show.
Reporting in Science Translational Medicine, medical investigators in France write that children with the genetic condition known as recessive dystrophic epidermolysis bullosa—RDEB—had immune responses and clinical severity shaped by skin-adapted S. aureus.
How S. aureus complicates RDEB
S. aureus exists in a multitude of strains, some antibiotic resistant and more dangerous than others. Scientists classify strains based on their genetic composition, whether they repel antibiotics or produce toxins. In RDEB, S. aureus causes blisters. The more dangerous the strain, the more complicated the condition of the affected child.
“Despite the well-described association of skin lesions with Staphylococcus aureus, the distinct ability of clinical isolates to influence the local and systemic inflammatory response in a patient-specific manner is insufficiently characterized,” writes Dr. Anne Jamet, lead author of the research.
“In this study, we analyzed clinical recessive dystrophic epidermolysis bullosa, RDEB, which is characterized by wounds chronically colonized with S. aureus, to explore the relationship between inflammatory immune response and strain diversity,” added Jamet of Université Paris Cité.
RDEB causes blisters and wounds because of a mutation in the COL7A1 gene of affected children. S. aureus exploits the mutation, ensuring its survival as it attacks and colonizes the mucous membranes and other sites throughout the body, especially the skin. Children with RDEB develop blisters of the mouth and esophagus, which can lead to difficulty with eating and swallowing.
Scarring can occur at any site where the bacteria have colonized and damaged healthy tissue. Blisters on the hands and feet ultimately can result in scarring that causes the fusion of fingers or toes. In severe disease, contracture of the hands and feet occurs. Joint deformities are also a possibility among those with severe RDEB, as is an elevated risk of aggressive skin cancer.
The immune system’s response to infection
The situation is made all the more difficult in RDEB by the way the bacterial disease hijacks the immune system with elevated activity of at least two key immune system components in severe disease.
Under normal conditions, the immune system communes with commensal bacteria—the so-called good bacteria—on the skin and elsewhere in the body while keeping pathogens out. Although some strains of S. aureus are pathogenic, others are commensals, a vital member of the skin microbiome. S. aureus, for example, is a common commensal colonizer of the nasal passages.
“The host immune system is involved in constant dialog with skin commensal microorganisms while simultaneously preventing the entry of pathogens,” Jamet wrote. “This interaction becomes critical when skin integrity is constitutively altered, as in genetic skin diseases associated with recurrent, chronic, nonhealing wounds.”
Study design and key findings
To find out what goes awry in the immune system of those with RDEB, allowing S. aureus to sustain colonization in the mouth, on the hands and feet, or any tissue of children with RDEB, the team of scientists designed and carried out a clinical trial.
Jamet and colleagues enrolled five children with moderate RDEB, 10 with severe disease, and 18 healthy children in their study to find answers. The team analyzed 30 subsets of immune cells and 800 different proteins in plasma.
Their findings showed that children with severe RDEB displayed a distinct immune signature marked by elevated quantities of CD4+ T cells and mucosal-associated invariant T—MAIT—cells that expressed interleukin-17A, an inflammatory signaling molecule.
“The genetic fragility of the skin of patients with RDEB combined with immune response anomalies result in chronic wounds that are chronically infected by S. aureus,” Jamet explained in the research paper. “The implication of S. aureus in RDEB severity is supported by the correlation of wound burden with S. aureus abundance.
“Our results could provide a rationale to test [monoclonal antibodies] in patients with severe RDEB,” Jamet wrote in conclusion, noting that antibodies that target interleukin-17A can be effective at combating chronic skin diseases.
Written for you by our author Delthia Ricks, edited by Gaby Clark, —this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive.
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More information:
Anne Jamet et al, Immune response and clinical severity are shaped by skin-adaptedStaphylococcus aureusin chronically infected patients, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adq7985
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