Staphylococcus Aureus Infection in DOCK8 Deficiency

Abstract

Background: The majority of patients with DOCK8 deficiency suffer from Staphylococcal aureus skin infections and severe atopic dermatitis. Under specific pathogen-free (SPF) conditions, Dock8-/- mice skin has a normal baseline. The role of S. aureus colonization and infection in driving pathogenic skin manifestations in Dock8-/- mice skin is unclear. Objective: To determine the effect of S. aureus infection on DOCK8 deficient skin. Methods: Dock8-/- and WT mice were tape-stripped to mimic skin scratching 24 hours before the application of S. aureus labeled with a fluorescent dye. Bacterial burden was evaluated through daily fluorescent imaging. Three days post-infection, the skin was examined by punch biopsy for quantitative analysis of colony-forming units (CFU) of S. aureus. The skin cellular infiltration was analyzed through histology and flow cytometry. Cytokine mRNA expression in the skin was determined using RT-qPCR. Results: Dock8-/- mice had a statistically significant increase in bacterial burden compared to WT mice shown by delayed clearance of fluorescent signals and higher CFU counts. There were significantly lower gd T cell numbers in Dock8-/- mice skin and higher CD8+ T cell infiltration on day three after S. aureus infection compared to WT controls. RT-qPCR showed lower Il17a and higher Ifng and Il22 expression in the skin. Histological analysis showed a marked increase of epidermal thickness in Dock8-/- mice compared to controls. Conclusion: The higher risk of S. aureus infection in DOCK8 deficiency may be caused by low numbers of IL-17A producing gd T cells that lead to a decrease in bacterial clearance.