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

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.

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10.

BACKGROUND: Atopic dermatitis (AD) is a T cell-mediated inflammatory skin disease, with TH2 cells initiating acute flares. This inflamed skin is immediately colonized with Staphylococcus aureus, which provides potent Toll-like receptor (TLR) 2 ligands. However, the effect of TLR2 ligands on the development of TH2-mediated AD inflammation remains unclear. OBJECTIVE: We investigated the progression of TH2 cell-mediated dermatitis after TLR2 activation. METHODS: Using models for acute AD with TH2 cells initiating cutaneous inflammation, we investigated the consequences of TLR2 activation. Dermatitis, as assessed by changes in ear skin thickness and histology, was analyzed in different BALB/c and C57BL/6 wild-type and knockout mouse strains, and immune profiling was carried out by using in vitro and ex vivo cytokine analyses. RESULTS: We show that TH2 cell-mediated dermatitis is self-limiting and depends on IL-4. Activation of TLR2 converted the limited TH2 dermatitis to chronic cutaneous inflammation. We demonstrate that the concerted activation of TLR2 and IL-4 receptor on dendritic cells is sufficient for this conversion. As an underlying mechanism, we found that the combinatorial sensing of the innate TLR2 ligands and the adaptive TH2 cytokine IL-4 suppressed anti-inflammatory IL-10 and consequently led to the exacerbation and persistence of dermatitis. CONCLUSION: Our data demonstrate that innate TLR2 signals convert transient TH2 cell-mediated dermatitis into persistent inflammation, as seen in chronic human AD, through IL-4-mediated suppression of IL-10. For the first time, these data show how initial AD lesions convert to chronic inflammation and provide another rationale for targeting IL-4 in patients with AD, a therapeutic approach that is currently under development.

Biological false-positive tests comprise a high proportion of Venereal Disease Research Laboratory reactions in an analysis of 300,000 sera.

This retrospective study on syphilis screening at the sexually transmitted infection (STI) unit of a University Department emphasizes the necessity of a treponemal-specific test as the appropriate screening test. The Venereal Disease Research Laboratory (VDRL) test for syphilis screening may, under certain circumstances, yield positive results in patients not infected with Treponema pallidum, a phenomenon referred to as biological false-positive (BFP) VDRL test. The aim of this study was to determine the frequency of BFP tests in a large sample of sera. In this retrospective study, we analysed the results of parallel VDRL and T. pallidum haemagglutination (TPHA) testing of a total of 514,940 blood samples obtained from patients at the Vienna General Hospital between January 1988 and November 1999. Patients' sera with incomplete data on stage and sex and duplicate sera were excluded, leaving 300,000 sera for analysis. The seroprevalence for syphilis was 1.77% (n = 5320), as determined by a positive TPHA test. It was significantly higher in male than in female patients (2.03% versus 1.58%, P<0.001). Of the patients reactive in the TPHA test, 3257 (61.2%) were negative in the VDRL. With regard to reactivity in VDRL testing, 2799 patients (0.92%) of the study population were positive, of whom 736 (26%) were biological false positive. BFP reactivity was found in 0.24% of all patients and was significantly higher in women than in men (0.27% versus 0.20%, P<0.001) and in patients over 60 years of age (0.34%) as compared with those under 60 (0.25%, P<0.001). This proportion might be even higher, as reactivity in the VDRL at 1:0 and 1:2 dilutions without a positive treponemal test was not reported. The subgroup of HIV-positive patients (n = 1415) revealed a 10-fold higher rate of BFP tests (2.1% versus 0.24), an effect being statistically significant. In a low syphilis prevalence population, BFP reactions comprise a high proportion of all VDRL reactors. Therefore, the use of the VDRL as a screening procedure is challenged.

[Alopecia areata universalis and disseminated mollusca contagiosa in atopic dermatitis. Hair re-growth during treatment with interferon gamma--therapeutic effect or coincidence?]. / Alopecia areata universalis und ausgedehnte Mollusca contagiosa bei atopischer Dermatitis: wieder einsetzendes Haarwachstum unter Behandlung mit Interferon gamma--echter Therapieeffekt oder Koinzidenz?

A 35-year-old woman presented with severe recalcitrant atopic dermatitis, in association with disseminated mollusca contagiosa and alopecia areata universalis. After several weeks of systemic interferon gamma, which was administered subcutaneously,the viral infection cleared and, surprisingly, four weeks after starting treatment hair re-growth was observed. Complete remission of alopecia areata was documented few weeks later and persists. After four cycles of high-dose intravenous immunoglobulin, a sustained remission of the atopic dermatitis was achieved.