Topical Mupirocin Treatment Reduces Interferon and Myeloid Signatures in Cutaneous Lupus Erythematous Lesions Through Targeting of Staphylococcus Species

Abstract

Objective

Cutaneous lupus erythematosus (CLE) is an inflammatory skin manifestation of systemic lupus erythematosus. Type I interferons (IFNs) promote inflammatory responses and are elevated in CLE lesions. We recently reported that CLE lesions are frequently colonized with Staphylococcus aureus. Here, we follow up via a proof-of-concept study to investigate whether type I IFN and inflammatory gene signatures in CLE lesions can be modulated with mupirocin, a topical antibiotic treatment against S aureus–mediated skin infections.

Methods

Participants with active CLE lesions (n = 12) were recruited and randomized into a week of topical treatment with either 2% mupirocin or petroleum jelly vehicle. Paired samples were collected before and after seven days of treatment to assess microbial lesional skin responses. Microbial samples from nares and lesional skin were used to determine baseline and posttreatment Staphylococcus abundance and microbial community profiles by 16S ribosomal RNA gene sequencing. Inflammatory responses were evaluated by bulk RNA sequencing of lesional skin biopsies.

Results

We identified 173 differentially expressed genes in CLE lesions after topical mupirocin treatment. Decreased lesional Staphylococcus burden correlated with decreased IFN pathway signaling and inflammatory gene expression and barrier dysfunction. Interestingly, mupirocin treatment lowered skin monocyte levels, and this mupirocin-associated depletion of monocytes correlated with decreased inflammatory gene expression.

Conclusion

Mupirocin treatment decreased lesional Staphylococcus, and this correlated with decreased IFN signaling and inflammatory gene expression. This study suggests a topical antibiotic could be employed to decrease lupus skin inflammation and type I IFN responses by reducing Staphylococcus colonization.