Staphylococcus aureus–derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2

Susanne Kaesler, Yuliya Skabytska, Ko Ming Chen, Wolfgang E. Kempf, Thomas Volz, Martin Köberle, Florian Wölbing, Ulrike Hein, Thomas Hartung, Carsten Kirschning, Martin Röcken, Tilo Biedermann

Research output: Contribution to journalArticle

Abstract

Background 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. Objective 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. Methods 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. Results 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. Conclusion We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.

Original languageEnglish (US)
Pages (from-to)780-790.e6
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number3
DOIs
StatePublished - Sep 1 2016

Keywords

  • Lipoteichoic acid
  • Staphylococcus aureus
  • T cell
  • atopic dermatitis
  • cell cycle
  • temporary unresponsiveness

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kaesler, S., Skabytska, Y., Chen, K. M., Kempf, W. E., Volz, T., Köberle, M., Wölbing, F., Hein, U., Hartung, T., Kirschning, C., Röcken, M., & Biedermann, T. (2016). Staphylococcus aureus–derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2. Journal of Allergy and Clinical Immunology, 138(3), 780-790.e6. https://doi.org/10.1016/j.jaci.2015.11.043