Abstract
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism, Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses. We analyzed antimicrobial protein P-2 expression in human skin at a single cell resolution using an amplified fluorescence in situ hybridization approach to detect P-2 mRNA in combination with immunophenotyping. We show that S. epidermidis activates GD T cells and upregulates P-2 in human skin ex vivo in a cell-specific manner. Furthermore, P-2 upregulation following S. epidermidis stimulation correlates with increased ability of skin cells to kill intracellular Staphylococcus aureus. Our findings are the first to reveal that skin commensal bacteria induce P-2 expression, which may be utilized beneficially to modulate host innate immune responses and protect from skin infections.
Highlights
Skin, in the same fashion as all other epithelial barrier sites harbors a distinct community of commensal microbes that modulate the host immune system [1,2,3]
We established an ex vivo skin model of S. epidermidis colonization to study the effect of this commensal microorganism on skin innate immune responses including Gamma delta (GD) T cell activity
We found a 6-7-fold induction in Fas ligand (FASLG) and Granulysin (GNLY) in S. epidermidis treated cells compared to control, untreated GD T cells (Figure 5B)
Summary
In the same fashion as all other epithelial barrier sites (gastrointestinal, reproductive, and respiratory tracts) harbors a distinct community of commensal microbes that modulate the host immune system [1,2,3]. In marked contrast to αβ T lymphocytes [24,25,26,27,28,29], GD T cells recognize antigens independently of peptide processing and major histocompatibility complex (MHC)restricted antigen presentation They are activated by signs of tissue stress, including infected or transformed cells, and respond by deploying an immediate and efficient killing response or by regulating the immune response against them. Phosphoantigens and several other molecules of microbial origin have been proposed as GD T cell antigens accounting for the specific recognition of infected cells These candidates include the Staphylococcus aureus superantigens Staphylococcal enterotoxin A (SEA) (and to a lesser extent staphylococcal enterotoxin E (SEE) [30, 31], which are recognized by the GD T cell receptor (TCR) independently from antigen processing and MHC presentation. The extent to which GD T cells promote cutaneous tissue physiology remains to be determined
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