Staphylococcus aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell–derived Cytokines

Abstract

<p class="first" id="d1999094e308"> <b>Rationale:</b> Chronic rhinosinusitis with nasal polyps is characterized by a T-helper cell type 2–skewed upper airway inflammation. Mucosal <i>Staphylococcus aureus</i> colonization is found in the majority of patients with nasal polyps. <i>S. aureus</i> is known to induce type 2 cytokine release via enterotoxins. </p><p id="d1999094e319"> <b>Objectives:</b> To investigate the impact of non–enterotoxin-producing <i>S. aureus</i> on type 2 cytokine release. </p><p id="d1999094e327"> <b>Methods:</b> TSLP (thymic stromal lymphopoietin), IL-33, and type 2 cytokines were assessed in a human mucosal tissue model upon <i>S. aureus</i> infection. </p><p id="d1999094e335"> <b>Measurements and Main Results:</b> <i>S. aureus</i> exposure increased the expression of IL-33, TSLP, IL-5, and IL-13 in nasal polyp tissue, accompanied by elevated expression levels of TSLP and IL-33 receptors, predominantly on CD3 ⁺ T cells. <i>S. aureus</i> infection led to the release of TSLP, but not IL-33, IL-5, or IL-13, from healthy inferior turbinate tissue. In contrast, <i>S. epidermidis</i> did not induce any epithelial cell–derived cytokines in nasal polyp or healthy tissue. <i>S. aureus</i> infection also increased the release of IL-33 and TSLP in BEAS-2B epithelial cells, accompanied by activation of NF-κB (nuclear factor κB) pathways. Incubation with CU-CPT22, a specific Toll-like receptor 2 antagonist, significantly reduced the <i>S. aureus</i>–induced release of TSLP and IL-33, and the activity of the NF-κB signal in BEAS-2B cells. </p><p id="d1999094e359"> <b>Conclusions:</b> This study demonstrates for the first time that <i>S. aureus</i> can directly induce epithelial cell–derived cytokine release via binding to Toll-like receptor 2, and may thereby propagate type 2 cytokine expression in nasal polyp tissue. </p>