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

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.

Membrane vesicles of Lacticaseibacillus rhamnosus JB-1 contain immunomodulatory lipoteichoic acid and are endocytosed by intestinal epithelial cells

“…They are important for bacterial physiology and host–bacteria interaction, and are commonly considered analogous to the gram-negative lipopolysaccharide, as both are studied as highly immunologically active molecules in host–bacteria interactions 38 . LTA are structurally variable between species 37 , and evidence is accumulating that LTA from some bacteria are immunoregulatory 31 , 39 – 42 .…”

Pre-digest of unprotected DNA by Benzonase improves the representation of living skin bacteria and efficiently depletes host DNA

“…Species typically isolated from the antecubital crease (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, and Micrococcus luteus) were included because the area is a predilection site of atopic dermatitis. This disease is an intensely studied inflammatory skin disorder with a still enigmatic role of lesional skin microbiota [29], which are not only seen as drivers of disease exacerbation but also contributors of anti-inflammatory stimuli [30][31][32]. Furthermore, typical skin-resident bacteria such as Corynebacterium pseudodiphthericum, Corynebacterium striatum, and Bacillus horneckiae as well as bacteria that can be found on the skin at lower abundance, like Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, were included.…”

Interactions between Host Immunity and Skin-Colonizing Staphylococci: No Two Siblings Are Alike

“…The IL-10-balanced immune profile of DCs exposed to epi-LTA was preserved in the presence of the Th2 hallmark cytokine IL-4. Although this should be tested in vivo, we can assume that S. epidermidis LTA does not contribute to enhanced cutaneous inflammation in an IL-4-rich environment, but rather regulates the inflammatory response [34]. Taken together, these studies suggest that modulation of S. epidermidis can be used to prevent skin diseases.…”