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 T_H2-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.