Staphylococcus Epidermis And Staphylococcus Aureus Differentialy Modulate Antimicrobial Molecule Perforin-2 During Wound Healing
Vivien Chen, Irena Pastar, Cheyanne R. Head, Katelyn O’Neill, Jamie Burgess, Natasa Strbo, Marjana Tomic-Canic.
University of Miami Miller School of Medicine, Miami, FL, USA.
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria, however its role in innate immune response to cutaneous pathogenic or beneficial microorganisms is largely unknown. We investigated P-2 expression pattern and cellular distribution in human skin, acute wound healing and in response to pathogenic Staphylococcus aureus or skin commensal S. epidermis. For this purpose we have established and utilized a novel approach for the measurement of P-2 mRNA within individual skin cells using an amplified fluorescence in situ hybridization (FISH) technique. The unique aspect of this approach is simultaneous detection of P-2 mRNA with immune-phenotyping for cell surface proteins. P-2 transcript was detected in both CD45+ and CD45- cutaneous cell populations. The highest level of P-2 was found in basal keratinocytes and gamma delta (GD) T cells. Utilizing human ex vivo wound model we show that wounding induces P-2 with the pick of expression at 48 h post wounding. In order to evaluate P-2 response to commensal and pathogenic bacteria, we developed human ex vivo wound infection model. The human tissue was sterilized to remove existing microflora, wounded and infected with either S. aureus or S. epidermidis. Infection of human wounds by S. aureus resulted in P-2 suppression predominantly in CD104+ keratinocytes, while in vitro P-2 overexpression resulted in reduction of intracellular bacterial load. In contrast to suppression by pathogenic bacteria, infection of human skin with commensal S. epidermis led to upregulation of P-2 and increase of the GDT cells frequency. Our findings reveal a novel P-2 mediated mechanism by which skin commensal bacteria may exert their beneficial role in modulating host innate immune response. In contrast to commensal bacteria, skin pathogens may escape cutaneous immunity through suppression of P-2 to cause persistent wound infections. Our ongoing studies focus on modulation of cutaneous immunity by commensal bacteria to prevent skin and wound infections.
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