Staphyloccoccus Aureus Induces a Th2 Response Via TSLP and IL-33 Release in Human Airway Mucosa

Abstract

S A T U R D A Y 259 Staphyloccoccus Aureus Induces a Th2 Response Via TSLP and IL-33 Release in Human Airway Mucosa Feng Lan, MD, Nan Zhang, Gabriele Holtappels, Natalie De Ruyck, Nikolaos G. Papadopoulos, MD, FAAAAI, EAACI President, Sebastian L. Johnston, MD, PhD, Claus Bachert, MD, PhD; Upper Airway Research Laboratory (URL), Ghent University Hospital, Ghent, Belgium, Allergy Research Center, Athens, Greece, Imperial College London, London, United Kingdom, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden. RATIONALE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is mainly characterized by a Th2-skewed inflammation. We hypothesized that S. aureus induces Th2 response in CRSwNP via epithelial derived cytokine production. METHODS: The levels of epithelial derived cytokines TSLP and IL-33 and consecutively Th2 cytokines were assessed in human mucosal S. aureus infection model. The localization of IL-33 and cell death in human CRSwNP tissue after S. aureus infection was evaluated by immunofluroscence staining. Human bronchial epithelial cell line BEAS-2B with S. aureus infection was examined for the epithelial cell-derived cytokine production pathway. RESULTS: The levels of TSLP and IL-5 significantly increased in supernatants of CRSwNP tissue after S. aureus infection. Even though an increased protein level of TSLP was found in control tissue after S. aureus infection, no change of IL-5 cytokine was observed. IL-33 was released into the extracellular space between epithelial cells, where TUNEL-positive cells were localized after S. aureus stimulation in CRSwNP tissue. At the same time, IL-33 cytokine was over-expressed in CRSwNP tissue homogenates after S. aureus infection. Increased levels of IL-33 and TSLP were induced by S. aureus in a dose-dependent manner in BEAS-2B cells with an increase phosphorylation process of p50, p65 and p38. CONCLUSIONS:Wehere demonstrate for the first time that S. aureuscan directly induces epithelial cell-derived cytokine in human nasal tissue, and propagates Th2 response only in CRSwNP tissue, not in controls. The NFkB and MAPK pathway might be involved in the production of TSLP and IL-33 after S. aureus infection.