Staphylococcus epidermidis facilitates intracellular pathogen clearance through upregulation of antimicrobial protein perforin-2 (P-2) in the human skin gamma delta T cells

Abstract

Abstract Staphylococcus epidermidis (SE), nonvirulent Gram-positive (G+) bacterium, is a member of the normal human skin microbiota with beneficial relationship with the host. Gamma delta (GD) T cells as the major T cell population in epithelial tissues have been implicated in maintaining tissue integrity, regulating inflammation and defending against pathogens. Perforin-2 (P-2) is a recently described antimicrobial protein responsible for clearance of intracellular G+ and G− bacteria. We examine the relationship between SE and P-2 expression in the human skin. Healthy human skin tissue was used for flow cytometric and bacterial infection analyses. We analyzed P-2 expression at a single cell resolution using an amplified fluorescence in situ hybridization (FISH) technique for detection of P-2 mRNA in combination with immune-phenotyping. Methicillin resistant Staphylococcus aureus (MRSA) intracellular killing assay was performed on the skin cells that were pretreated with S. epidermidis for 24 h. We found increase in the frequency of skin GDT cells and induction of P-2 transcripts in GDT cells after S. epidermidis infection. Incubating skin cells with S. epidermidis for 24h prior infection with MRSA resulted in rapid intracellular clearance of MRSA. 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, establishment of S. aureus biofilm resulted in suppression of P-2 expression, revealing a mechanism by which S. aureus escapes cutaneous immunity to cause persistent biofilm wound infections.