Staphylococcus aureus and toll-like receptor activity in atopic dermatitis

Abstract

Introduction Staphylococcus aureus skin infections are an almost ubiquitous feature of patients with atopic dermatitis (AD). TLR1, 2 and 6 are important in immune sensing of these bacteria. The aim of this study was to determine whether defects in TLR1, 2 and/or 6 expression / function may explain the propensity to infection in humans and the NC eczema mouse model.Methods Fibroblast cell lines from severe AD, nonatopic controls, and mouse embryonic fibroblasts (MEFs) from the NC, MSM/Ms wild-type strain and a 3T3 control strain were studied. TLR1, 2 and 6 expression were measured by qPCR and FACS. IL-6, TNF-alpha, TSLP and IL-33 production was measured by qPCR and ELISA at baseline and after stimulation with LPS, HKSA and a live strain of Staphylococcus aureus that produced only SEB. Results No differences were found in either TLR expression or function in human fibroblasts derived from patients or controls. The MSM/Ms MEFs expressed significantly more TLR1 and 2, as well as exhibiting a high inflammatory profile after stimulation comparing with 3T3 and the NC MEFs. Live Staphylococcus aureus, but not HKSA, LPS or SEB, was a potent stimulus for Th2-inducing cytokines (TSLP and IL-33), and induced cell death. Cytokine levels were found to be similar in AD and NC MEFs when compared to healthy controls. Conclusion Eczema in both humans and the NC mouse is not associated with abnormalities in fibroblast TLR1, 2, and 6 expression or function. Live, but not killed Staphylococcus aureus or its enterotoxin, is a potent inducer of TSLP and IL-33 in both species.

Date of Award	1 Jan 1824
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Peter Arkwright (Supervisor) & Joanne Pennock (Supervisor)