Thymic Stromal Lymphopoietin is Induced by Respiratory Syncytial Virus-infected Airway Epithelial Cells and Promotes a Type 2 Response to Infection

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2012 Sep 18

PMID 22981788

Citations 107

Authors

Hai-Chon Lee

Mark B Headley

Yueh-Ming Loo

Aaron Berlin

Michael Gale Jr

Jason S Debley

Nicholas W Lukacs

Steven F Ziegler

Affiliations

Soon will be listed here.

Abstract

Background: Respiratory viral infection, including respiratory syncytial virus (RSV) and rhinovirus, has been linked to respiratory disease in pediatric patients, including severe acute bronchiolitis and asthma exacerbation.

Objective: The study examined the role of the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) in the response to RSV infection.

Methods: Infection of human airway epithelial cells was used to examine TSLP induction after RSV infection. Air-liquid interface cultures from healthy children and children with asthma were also tested for TSLP production after infection. Finally, a mouse model was used to directly test the role of TSLP signaling in the response to RSV infection.

Results: Infection of airway epithelial cells with RSV led to the production of TSLP via activation of an innate signaling pathway that involved retinoic acid induced gene I, interferon promoter-stimulating factor 1, and nuclear factor-κB. Consistent with this observation, airway epithelial cells from asthmatic children a produced significantly greater levels of TSLP after RSV infection than cells from healthy children. In mouse models, RSV-induced TSLP expression was found to be critical for the development of immunopathology.

Conclusion: These findings suggest that RSV can use an innate antiviral signaling pathway to drive a potentially nonproductive immune response and has important implications for the role of TSLP in viral immune responses in general.

Citing Articles

T1-T2 Interplay in the Complex Immune Landscape of Severe Asthma.

Gauthier M, Kale S, Ray A Immunol Rev. 2025; 330(1):e70011.

PMID: 39991821 PMC: 11849004. DOI: 10.1111/imr.70011.

Unspecified asthma, childhood-onset, and adult-onset asthma have different causal genes: a Mendelian randomization analysis.

Zaied R, Gokuladhas S, Walker C, OSullivan J Front Immunol. 2024; 15:1412032.

PMID: 39628479 PMC: 11611866. DOI: 10.3389/fimmu.2024.1412032.

MERS-CoV Infection and Its Impact on the Expression of TSLP Cytokine and IgG Antibodies: An In Vivo and In Vitro Study.

Mubarak A, Alqoufail M, Almutairi S, Alrfaei B, Almotairi A, Aziz I Infect Drug Resist. 2024; 17:4589-4598.

PMID: 39469096 PMC: 11513571. DOI: 10.2147/IDR.S483133.

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma.

Djeddi S, Fernandez-Salinas D, Huang G, Aguiar V, Mohanty C, Kendziorski C Cell Genom. 2024; 4(9):100636.

PMID: 39197446 PMC: 11480861. DOI: 10.1016/j.xgen.2024.100636.

Early-life risk factors which govern pro-allergic immunity.

Ptaschinski C, Gibbs B Semin Immunopathol. 2024; 46(3-4):9.

PMID: 39066790 PMC: 11283399. DOI: 10.1007/s00281-024-01020-x.

References

Loo Y, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L . Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol. 2007; 82(1):335-45. PMC: 2224404. DOI: 10.1128/JVI.01080-07. View

Bendelja K, Gagro A, Bace A, Krsulovic-Hresic V, Drazenovic V, Mlinaric-Galinovic G . Predominant type-2 response in infants with respiratory syncytial virus (RSV) infection demonstrated by cytokine flow cytometry. Clin Exp Immunol. 2000; 121(2):332-8. PMC: 1905700. DOI: 10.1046/j.1365-2249.2000.01297.x. View

Rudd B, Smit J, Flavell R, Alexopoulou L, Schaller M, Gruber A . Deletion of TLR3 alters the pulmonary immune environment and mucus production during respiratory syncytial virus infection. J Immunol. 2006; 176(3):1937-42. DOI: 10.4049/jimmunol.176.3.1937. View

Qiao J, Li A, Jin X . TSLP from RSV-stimulated rat airway epithelial cells activates myeloid dendritic cells. Immunol Cell Biol. 2010; 89(2):231-8. DOI: 10.1038/icb.2010.85. View

Hammad H, Chieppa M, Perros F, Willart M, Germain R, Lambrecht B . House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med. 2009; 15(4):410-6. PMC: 2789255. DOI: 10.1038/nm.1946. View

Taylor B, Zaph C, Troy A, Du Y, Guild K, Comeau M . TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med. 2009; 206(3):655-67. PMC: 2699121. DOI: 10.1084/jem.20081499. View

Carpino N, Thierfelder W, Chang M, Saris C, Turner S, Ziegler S . Absence of an essential role for thymic stromal lymphopoietin receptor in murine B-cell development. Mol Cell Biol. 2004; 24(6):2584-92. PMC: 355866. DOI: 10.1128/MCB.24.6.2584-2592.2004. View

Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H . IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005; 6(10):981-8. DOI: 10.1038/ni1243. View

Chang J, Braciale T . Respiratory syncytial virus infection suppresses lung CD8+ T-cell effector activity and peripheral CD8+ T-cell memory in the respiratory tract. Nat Med. 2002; 8(1):54-60. DOI: 10.1038/nm0102-54. View

10.

Erjefalt J . The airway epithelium as regulator of inflammation patterns in asthma. Clin Respir J. 2010; 4 Suppl 1:9-14. DOI: 10.1111/j.1752-699X.2010.00191.x. View

11.

Kristjansson S, Bjarnarson S, Wennergren G, Palsdottir A, Arnadottir T, Haraldsson A . Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local TH2-like response. J Allergy Clin Immunol. 2005; 116(4):805-11. DOI: 10.1016/j.jaci.2005.07.012. View

12.

Shikotra A, Choy D, Ohri C, Doran E, Butler C, Hargadon B . Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J Allergy Clin Immunol. 2011; 129(1):104-11.e1-9. DOI: 10.1016/j.jaci.2011.08.031. View

13.

Zhou B, Headley M, Aye T, Tocker J, Comeau M, Ziegler S . Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses. J Immunol. 2008; 181(9):6557-62. PMC: 2878483. DOI: 10.4049/jimmunol.181.9.6557. View

14.

Soumelis V, Reche P, Kanzler H, Yuan W, Edward G, Homey B . Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002; 3(7):673-80. DOI: 10.1038/ni805. View

15.

Johnston S, Pattemore P, SANDERSON G, Smith S, Lampe F, Josephs L . Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ. 1995; 310(6989):1225-9. PMC: 2549614. DOI: 10.1136/bmj.310.6989.1225. View

16.

Johnson C, Gale Jr M . CARD games between virus and host get a new player. Trends Immunol. 2005; 27(1):1-4. DOI: 10.1016/j.it.2005.11.004. View

17.

Kato A, Favoreto Jr S, Avila P, Schleimer R . TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells. J Immunol. 2007; 179(2):1080-7. PMC: 2220044. DOI: 10.4049/jimmunol.179.2.1080. View

18.

Grainge C, Lau L, Ward J, Dulay V, Lahiff G, Wilson S . Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011; 364(21):2006-15. DOI: 10.1056/NEJMoa1014350. View

19.

Kato A, Schleimer R . Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity. Curr Opin Immunol. 2007; 19(6):711-20. PMC: 2196222. DOI: 10.1016/j.coi.2007.08.004. View

20.

Kassim S, Gharib S, Mecham B, Birkland T, Parks W, McGuire J . Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa. Infect Immun. 2007; 75(12):5640-50. PMC: 2168342. DOI: 10.1128/IAI.00799-07. View