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Staphylococcus Aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines

Staphylococcus Aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines

Feng Lan, Nan Zhang, Gabriele Holtappels, Natalie De Ruyck, Olga Krysko, Koen Van Crombruggen, Harald Braun, Sebastian L Johnston, Nikos G Papadopoulos, Luo Zhang, Claus Bachert

Am J Respir Crit Care Med. 2018 Aug 15;198(4):452-463.

PMID: 29768034

Abstract:

Rationale:
Chronic rhinosinusitis with nasal polyps is characterized by a T-helper cell type 2-skewed upper airway inflammation. Mucosal Staphylococcus aureus colonization is found in the majority of patients with nasal polyps. S. aureus is known to induce type 2 cytokine release via enterotoxins.
Objectives:
To investigate the impact of non-enterotoxin-producing S. aureus on type 2 cytokine release.
Methods:
TSLP (thymic stromal lymphopoietin), IL-33, and type 2 cytokines were assessed in a human mucosal tissue model upon S. aureus infection.
Measurements and main results:
S. aureus 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. S. aureus infection led to the release of TSLP, but not IL-33, IL-5, or IL-13, from healthy inferior turbinate tissue. In contrast, S. epidermidis did not induce any epithelial cell-derived cytokines in nasal polyp or healthy tissue. S. aureus 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 S. aureus-induced release of TSLP and IL-33, and the activity of the NF-κB signal in BEAS-2B cells.
Conclusions:
This study demonstrates for the first time that S. aureus 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1416324850	CU-CPT22		1416324-85-0	Price

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