@article{0398dd215abe4bd49c07a8e610e23b66,
title = "Staphylococcus aureus–derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2",
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.",
keywords = "Lipoteichoic acid, Staphylococcus aureus, T cell, atopic dermatitis, cell cycle, temporary unresponsiveness",
author = "Susanne Kaesler and Yuliya Skabytska and Chen, {Ko Ming} and Kempf, {Wolfgang E.} and Thomas Volz and Martin K{\"o}berle and Florian W{\"o}lbing and Ulrike Hein and Thomas Hartung and Carsten Kirschning and Martin R{\"o}cken and Tilo Biedermann",
note = "Funding Information: Supported by contract research “Allergologie 2” of the Baden-W{\"u}rttemberg Stiftung (P-LS-AL2/4) and by grants of the Deutsche Forschungsgemeinschaft (DFG; BI696/10-1 , B1696/5-1 , BI696/5-2 , SFB 685 A06, C01 , SFB 824 B10 ) and Wilhelm Sander-Stiftung ( 2012.056.1 ). Funding Information: Disclosure of potential conflict of interest: S. Kaesler has received grants from Landesstiftung Baden-W{\"u}rttemberg and Deutsche Forschungsgemeinschaft. K.-M. Chen has received a grant from Baden-W{\"u}rttemberg Stiftung. T. Volz has received payment for lectures from La Roche Posay. M. K{\"o}berle has received grants from Deutsche Forschungsgemeinschaft (B1696/5-1, BI696/5-2). U. Hein has received a grant from Landesstiftung Baden-W{\"u}rttemberg. M. R{\"o}cken has received grants from Deutsche Forschungsgemeinschaft (SFB TRR 156/1 TP B 06, RO 764/15-1 AOBJ); has consultant arrangements with Almirall Hermal, Biogen Idec, and Regeneron; is employed by Government Baden-W{\"u}rttemberg; has a pending patent (DE 10 2012 024 749.4); and has received travel support from Deutsche Dermatologische Gesellschaft e. V. and European Academy of Dermatology and Venereology. T. Biedermann has received grants from Deutsche Forschungsgemeinschaft (BI696/10-1, B1696/5-1, BI696/5-2, SFB 685, SFB 824), Helmholtz, Novartis, and Phadia; has received payment for development of educational presentations from Phadia; and has consultant arrangements with Alk-Abell{\'o}, Astellas, Bencard, Biogen, Janssen, Leo, Meda, MSD, Novartis, Phadia, and Thermo Fisher. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: {\textcopyright} 2016 American Academy of Allergy, Asthma & Immunology",
year = "2016",
month = sep,
day = "1",
doi = "10.1016/j.jaci.2015.11.043",
language = "English (US)",
volume = "138",
pages = "780--790.e6",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",
}