Atopic Dermatitis–like mouse model using early inoculation of patient-derived S. aureus together with MC903

TL;DR

This study explores how different strains of Staphylococcus aureus from atopic dermatitis patients affect skin inflammation in mice, especially in a type 2 immune environment.

Contribution

The study introduces a novel mouse model using patient-derived S. aureus strains to investigate their role in AD inflammation.

Findings

Clinical S. aureus strains showed significant variability in their ability to cause inflammation.

S. aureus strains enhanced colonization and inflammation in a type 2 immune environment.

S. epidermidis strains induced only mild and consistent inflammation with less strain variability.

Abstract

Staphylococcus aureus (S. aureus) worsens atopic dermatitis (AD), but how individual strains differ in pathogenicity remains unclear. Mouse models that mimic AD and allow direct manipulation of S. aureus in early stages of disease are limited. Moreover, these models rarely incorporate clinical S. aureus strains isolated from patients with AD. In this study, we investigated the inflammatory potential of clinical S. aureus and S. epidermidis isolates from patients with AD in a mouse model. Clinical S. aureus strains showed significant variability in their ability to elicit inflammation. The inflammation was associated with differences in virulence factor expression and, to a lesser extent, with genomic variation. In contrast, S. epidermidis strains (taken from the same lesional skin sites of patients) induced only mild but consistent inflammation, with less variability at the strain level. Next, we examined the impact of a pathogenic clinical S. aureus strains in the presence of an MC903-induced type 2 immune environment. Under these conditions, S. aureus enhanced colonization; increased inflammation; and promoted type 1, type 2, and type 17/22 immune responses. These responses were less evident with either treatment alone. Our findings suggest that clinical S. aureus strains from patients with AD differ in their capacity to modulate skin inflammation, particularly within a type 2–skewed environment. These results highlight the potential value of incorporating clinically relevant S. aureus isolates into early-stage in vivo models to better understand AD immunopathology and to inform microbiome-targeted therapeutic strategies.

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