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

Abstract

Background<br /><br />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.<br /><br />Objective<br /><br />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.<br /><br />Methods<br /><br />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 T_H2-mediated cutaneous inflammation.<br /><br />Results<br /><br />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.<br /><br />Conclusion<br /><br />We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.