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Staphylococcus aureus induces a mucosal type 2 immune response via epithelial cell-derived cytokines

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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-kappa B (nuclear factor kB) 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 theNF-kappa B 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.
Keywords
chronic rhinosinusitis with nasal polyps, IL-33, Staphylococcus aureus, Th2, thymic stromal lymphopoietin, THYMIC STROMAL LYMPHOPOIETIN, NASAL POLYP DISEASE, CHRONIC RHINOSINUSITIS, HUMAN KERATINOCYTES, ENTEROTOXIN-B, INFLAMMATION, ASTHMA, IL-33, PROTEIN, TSLP

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MLA
Lan, Feng, Nan Zhang, Gabriële Holtappels, et al. “Staphylococcus Aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines.” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 198.4 (2018): 452–463. Print.
APA
Lan, Feng, Zhang, N., Holtappels, G., De Ruyck, N., Krysko, O., Van Crombruggen, K., Braun, H., et al. (2018). Staphylococcus aureus induces a mucosal type 2 immune response via epithelial cell-derived cytokines. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 198(4), 452–463.
Chicago author-date
Lan, Feng, Nan Zhang, Gabriële Holtappels, Natalie De Ruyck, Olga Krysko, Koen Van Crombruggen, Harald Braun, et al. 2018. “Staphylococcus Aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines.” American Journal of Respiratory and Critical Care Medicine 198 (4): 452–463.
Chicago author-date (all authors)
Lan, Feng, Nan Zhang, Gabriële Holtappels, Natalie De Ruyck, Olga Krysko, Koen Van Crombruggen, Harald Braun, Sebastian L Johnston, Nikos G Papadopoulos, Luo Zhang, and Claus Bachert. 2018. “Staphylococcus Aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines.” American Journal of Respiratory and Critical Care Medicine 198 (4): 452–463.
Vancouver
1.
Lan F, Zhang N, Holtappels G, De Ruyck N, Krysko O, Van Crombruggen K, et al. Staphylococcus aureus induces a mucosal type 2 immune response via epithelial cell-derived cytokines. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2018;198(4):452–63.
IEEE
[1]
F. Lan et al., “Staphylococcus aureus induces a mucosal type 2 immune response via epithelial cell-derived cytokines,” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 198, no. 4, pp. 452–463, 2018.
@article{8582199,
  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-kappa B (nuclear factor kB) 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 theNF-kappa B 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.},
  author       = {Lan, Feng and Zhang, Nan and Holtappels, Gabriële and De Ruyck, Natalie and Krysko, Olga and Van Crombruggen, Koen and Braun, Harald and Johnston, Sebastian L and Papadopoulos, Nikos G and Zhang, Luo and Bachert, Claus},
  issn         = {1073-449X},
  journal      = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
  keywords     = {chronic rhinosinusitis with nasal polyps,IL-33,Staphylococcus aureus,Th2,thymic stromal lymphopoietin,THYMIC STROMAL LYMPHOPOIETIN,NASAL POLYP DISEASE,CHRONIC RHINOSINUSITIS,HUMAN KERATINOCYTES,ENTEROTOXIN-B,INFLAMMATION,ASTHMA,IL-33,PROTEIN,TSLP},
  language     = {eng},
  number       = {4},
  pages        = {452--463},
  title        = {Staphylococcus aureus induces a mucosal type 2 immune response via epithelial cell-derived cytokines},
  url          = {http://dx.doi.org/10.1164/rccm.201710-2112oc},
  volume       = {198},
  year         = {2018},
}

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