title: Staphylococcus aureus-derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2.
abstract: The interplay between microbes and surface organs, such as the skin, shapes a complex immune system with several checks and balances. The first-line defense is mediated by innate immune pathways leading to inflammation. In the second phase specific T cells invade the infected organ, amplifying inflammation and defense. Consecutively, termination of inflammation is crucial to avoid chronic inflammation triggered by microbes, such as in patients with atopic dermatitis.
  
  
  
  We aimed to elucidate how the Staphylococcus aureus-derived cell-wall component lipoteichoic acid (LTA) governs the second phase of immune responses when high concentrations of LTA access T cells directly through disrupted skin.
  
  
  
  We analyzed the direct exposure of T cells to LTA in vitro. For in vivo analyses, we used fluorescein isothiocyanate contact hypersensitivity and ovalbumin-induced dermatitis as models for TH2-mediated cutaneous inflammation.
  
  
  
  We observed that LTA potently suppressed T-lymphocyte activation in a Toll-like receptor 2-independent manner. LTA-exposed T cells did not proliferate and did not produce cytokines. Importantly, these T cells remained completely viable and were responsive to consecutive activation signals on subsequent removal of LTA. Thus LTA exposure resulted in temporary functional T-cell paralysis. In vivo experiments revealed that T-cell cytokine production and cutaneous recall responses were significantly suppressed by LTA.
  
  
  
  We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kaesler
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Skabytska
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Derma Labor Düsseldorf, Dusseldorf, Germany.
authors.forename: Ko-Ming
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Kempf
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Volz
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Köberle
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wölbing
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hein
authors.affiliation: Center for Alternatives to Animal Testing Europe, University of Konstanz, Konstanz, Germany; Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Md.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.affiliation: Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kirschning
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr, Tubingen, Germany; Department of Dermatology and Allergology, Technische Universität München, Munich, Germany. Electronic address: Tilo.Biedermann@tum.de.
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
mesh_terms: D000485:Allergens; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010047:Ovalbumin; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013682:Teichoic Acids / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate
keywords: Lipoteichoic acid; Staphylococcus aureus; T cell; atopic dermatitis; cell cycle; temporary unresponsiveness