Format

Send to

Choose Destination
Exp Dermatol. 2018 Apr;27(4):318-326. doi: 10.1111/exd.13540.

Induction of IL-10-balanced immune profiles following exposure to LTA from Staphylococcus epidermidis.

Author information

1
Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.
2
Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
3
Center for Alternatives to Animal Testing Europe, University of Konstanz, Konstanz, Germany.
4
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
5
Clinical Unit Allergology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.

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 LTAs was analysed. Exposure to epi-LTA or aureus-LTA activated human immune cells and murine dendritic cells (DCs) via TLR2/MyD88, however, resulting in divergent immune profiles. Differences between LTAs 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 DCs activated CD4+ T cells; however, while T-cell-derived IL-10 was equivalent between LTAs, IFN-γ and IL-17 were significantly higher for aureus-LTA. Mimicking acute AD by exposing DCs to IL-4 and LTAs 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 DCs 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 LTAs. Epi-LTA induced IL-10-balanced, aureus-LTA pro-inflammatory immune profiles.

KEYWORDS:

atopic dermatitis; cytokines; dendritic cells; lipoteichoic acid; microbial dysbiosis

PMID:
29569765
DOI:
10.1111/exd.13540

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center