Julianne Clowry

Calcium is a critical regulator of Staphylococcus aureus skin adhesion, stabilizing one of the strongest noncovalent biomolecular interactions ever recorded. Using in vitro and in silico single-molecule force spectroscopy, we demonstrate that calcium ions (Ca ²⁺ ) are essential for the ultrastrong binding between the serine-aspartate repeat protein D (SdrD) adhesin and the human skin protein desmoglein-1 (DSG-1), withstanding forces exceeding 2 nanonewtons. Ca ²⁺ ions stabilize both the SdrD complex and the mechanically robust SdrD B-domains, which exhibit unprecedented folding strength. In the context of atopic dermatitis (AD), disrupted calcium gradients amplify SdrD interactions, which could potentially intensify S. aureus virulence. Furthermore, abnormal DSG-1 distribution on AD-affected skin enhances bacterial adhesion. These findings provide crucial insights into the calcium-dependent regulation of bacterial adhesion and folding, suggesting possible therapeutic targets to combat S. aureus infections.

Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S . aureus have had limited efficacy and S . aureus –associated temporal disease flares are synonymous with AD. An alternative approach is an anti– S . aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti– S . aureus responses; however, correlates of T cell immunity against S . aureus in AD have not been identified. We identify a systemic and cutaneous immunological signature associated with S . aureus skin infection ( AD _S.aureus ) in a pediatric AD cohort, using a combined Bayesian multinomial analysis. AD _S.aureus was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct Th1 and Th2 cells to skin. Systemic CD4 ⁺ and CD8 ⁺ T cells, except for Th2 cells, were suppressed in AD _S.aureus , particularly circulating Th1, memory IL-10 ⁺ T cells, and skin-homing memory Th17 cells. Systemic γδ T cell expansion in AD _S.aureus was also observed. This study suggests that augmentation of protective T cell subsets is a potential therapeutic strategy in the management of S . aureus in AD.

Staphylococcus aureus exacerbates barrier dysfunction and immune dysregulation in atopic dermatitis (AD) leading to disease flares. There is an u | POSTER

To the Editor:A 72-year-old man presented with symptomatic anemia and nonpalpable purpura of the legs, abdomen, and arms of 2 weeks’ duration (Figure 1). There

Background Dimethyl fumarate (DMF) is the active ingredient of Skilarence™ and Tecfidera™ which are used for the treatment of psoriasis and multiple sclerosis, respectively. Various immunomodulatory mechanisms of action have been identified for DMF; however, it is still unclear what effects DMF exerts in vivo in psoriasis patients. Aim In this study we examined the effects of DMF, both in vivo and in vitro, on T cells which play a key role in the pathogenesis of psoriasis. Methods The frequency of T cell subsets was examined by flow cytometry in untreated psoriasis patients or those treated with DMF. The effects of DMF in vitro on T cell survival, activation and proliferation and cell surface thiols were assessed by flow cytometry. Results In psoriasis patients treated with DMF we observed an increase in the frequency of Treg cells and a decrease in Th17 lineage cells and associated cytokines IL‐17, IL‐22 and GM‐CSF. T cells cultured in vitro with DMF exhibited reduced viability and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. However, the frequency of Treg cells increased in the presence of DMF due to their heightened ability to resist DMF‐induced oxidative stress. Conclusions DMF enhanced the ratio of Treg:Th17 cells both in psoriasis patients, multiple sclerosis patients and in vitro. Furthermore, our data suggest that this is at least in part as a result of the differential effects of DMF on Treg compared with T conventional cells.