Induction of IL IL ‐10‐balanced immune profiles following exposure to LTA LTA from Staphylococcus?epidermidis Staphylococcus?epidermidis

摘要

Abstract Staphylococcus?epidermidis colonises human skin without apparent inflammation, but a dominance of S.?epidermidis and S.?aureus is characteristic of cutaneous microbial dysbiosis in atopic dermatitis ( AD ). While S.?aureus can trigger AD , the role of S.?epidermidis is less understood. We characterised consequences of innate immune sensing of lipoteichoic acid ( LTA ) preparations derived from S.?epidermidis (epi‐ LTA ) or S.?aureus (aureus‐ LTA ). Therefore, dendritic cell ( DC ) activation and consecutive priming of antigen‐specific T cells following exposure of DC to epi‐ LTA or aureus‐ LTA were investigated. Mimicking acute AD , exposure of DC to IL ‐4 and LTA s was analysed. Exposure to epi‐ LTA or aureus‐ LTA activated human immune cells and murine dendritic cells ( DC s) via TLR 2/MyD88, however, resulting in divergent immune profiles. Differences between LTA s were significant for IL ‐6, IL ‐12p40 and IL ‐12p70 but not for IL ‐10, which was best reflected by the IL ‐12p70‐to‐ IL ‐10 ratio being IL ‐10‐balanced for epi‐ LTA but pro‐inflammatory for aureus‐ LTA . LTA ‐exposed DC s activated CD 4+ T cells; however, while T‐cell‐derived IL ‐10 was equivalent between LTA s, IFN ‐γ and IL ‐17 were significantly higher for aureus‐ LTA . Mimicking acute AD by exposing DC s to IL ‐4 and LTA s revealed that IL ‐4 significantly and uniformly suppressed epi‐ LTA ‐induced cytokine production, keeping the IL ‐12p70‐to‐ IL ‐10 ratio balanced. In contrast, exposure of DC s to aureus‐ LTA and IL ‐4 enhanced IL ‐12p70 but suppressed IL ‐10 levels, further unbalancing the IL ‐12p70‐to‐ IL ‐10 ratio. These data demonstrate opposing immune consequences following exposure to staphylococcal LTA s. Epi‐ LTA induced IL ‐10‐balanced, aureus‐ LTA pro‐inflammatory immune profiles.