Tissue microenvironment initiates an immune response to structural components of Staphylococcus aureus

Abstract

Cell-to-cell communication in skin participates to the maintenance of homeostatic responses to foreign substances. Certain strains of Staphylococcus (S) aureus are vicious pathogens that cause deleterious effects in host cells and tissues. Both secreted toxins and structural components of S. aureus trigger an immune response, though how S. aureus stimulates host immune responses is poorly understood. We explored here how keratinocytes and fibroblasts initiate the first steps of an immune response by activating dendritic cells (DCs) through recognition of structural components of S. aureus. We treated monocyte-derived Langerhans cells (moLCs) and monocyte-derived DCs (moDCs) with conditioned media from keratinocytes (K-CM) and fibroblasts (F-CM) treated with heat-killed S. aureus (HKSA) respectively, or directly with HKSA. Immune and inflammatory responses from keratinocytes, fibroblasts, moLCs and moDCs were assessed by analysis of cell surface markers and cytokine production using flow cytometry, real-time PCR and ELISA assays. K-CM and F-CM increased the expression of CD86 and HLA-DR on moLCs and moDCs, in association with a specific cytokine profile. K-CM upregulated TNFA, IL-1B and GM-CSF mRNA expression in moLCs, while F-CM upregulated IL-12 and downregulated TNFA and TGFB mRNA expression in moDCs. Additionally, F-CM attenuated the induction of an inflammatory profile in monocytes. The recognition of structural components from S. aureus by cutaneous microenvironment induces the activation and the expression of specific cytokines from LCs and DCs.

Exploring the wound healing, anti-inflammatory, anti-pathogenic and proteomic effects of lactic acid bacteria on keratinocytes

“…A multidisciplinary approach, involving analytical chemistry, proteomics, biochemistry and microbiology, was applied to the analysis of HaCaT cells which represent a useful model to investigate repair response, anti-inflammatory interventions and infection of human keratinocytes 24 . This study was performed by treating HaCaT cells with LAB lysates since they offer a safer option than live bacteria for treatment of damaged skin 13,25 , and by using heat-killed pathogens since they still induce infection through their cell wall components 26 assuring greater feasibility in the co-culture experiments.…”