Effects of the Staphylococcus aureus and Staphylococcus epidermidis Secretomes Isolated from the Skin Microbiota of Atopic Children on CD4+ T Cell Activation

Abstract

Interactions between the immune system and skin bacteria are of major importance in the pathophysiology of atopic dermatitis (AD), yet our understanding of them is limited. From a cohort of very young AD children (1 to 3 years old), sensitized to Dermatophagoides pteronyssinus allergens (Der p), we conducted culturomic analysis of skin microbiota, cutaneous transcript profiling and quantification of anti-Der p CD4+ T cells. This showed that the presence of S. aureus in inflamed skin of AD patients was associated with a high IgE response, increased expression of inflammatory and Th2/Th22 transcripts and the prevalence of a peripheral Th2 anti-Der p response. Monocyte-derived dendritic cells (moDC) exposed to the S. aureus and S. epidermidis secretomes were found to release pro-inflammatory IFN-γ and anti-inflammatory IL-10, respectively. Allogeneic moDC exposed to the S. aureus secretome also induced the proliferation of CD4+ T cells and this effect was counteracted by concurrent exposure to the S. epidermidis secretome. In addition, whereas the S. epidermidis secretome promoted the activity of regulatory T cells (Treg) in suppressing the proliferation of conventional CD4+ T cells, the Treg lost this ability in the presence of the S. aureus secretome. We therefore conclude that S. aureus may cause and promote inflammation in the skin of AD children through concomitant Th2 activation and the silencing of resident Treg cells. Commensals such as S. epidermidis may counteract these effects by inducing the release of IL-10 by skin dendritic cells.

Biofilm Producing Staphylococcus epidermidis (RP62A Strain) Inhibits Osseous Integration Without Osteolysis and Histopathology in a Murine Septic Implant Model

“…6), despite the absence of inflammatory cells and bone marrow destruction. While similar gene expression findings have been reported for S. aureus infections 37,38 and S. epidermidis in vitro and in vivo studies, 39,40 the lack of osteolysis in this osteoclastogenic environment remains largely unexplained and remains an important future research direction.…”

Poly- N -Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect

“…The generation of Tregs with enhanced suppressive activity was also reported in studies related to other pathogens (22,46) and may thus be a general phenomenon associated with infectious conditions. Nevertheless, a previous study showed that extracellular products of S. epidermidis promoted the suppressive activity of human Tregs (47), further indicating that this cell population may be involved in counterinflammatory mechanisms operating during infections with this bacterium. Tregs were recently shown to be crucial for establishing S. epidermidis skin commensalism (48).…”

Homeostatic Immunity and the Microbiota

“…However, cutaneous microbes may also be able to promote regulatory responses in adult mice, as exposure to a lysate of Vitreoscilla filiformis can promote the accumulation of T reg cells within the skin (Volz et al, 2014). Further, secreted products from S. epidermidis promotes IL-10 production by human dendritic cells (Laborel-Preneron et al, 2015) and skin exposure to TLR2-6 binding S. aureus derived lipopeptides can potently suppress immune responses via the induction of regulatory myeloid cells (Skabytska et al, 2014). The microbiota can also limit Thymic strmal lymphopoietin (TSLP) expression in mice with a defective skin barrier (Yockey et al, 2013).…”