{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:01:14Z","timestamp":1771531274308,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human rhinoviruses (HRV) are a major cause of asthma exacerbations and hospitalization. Studies using primary cultures suggest that this may be due to impaired production of type I and type III IFNs by asthmatic bronchial epithelial cells. Although epithelial cells are the main target for HRV infection, HRV can be detected in the subepithelial layer of bronchial mucosa from infected subjects by in situ hybridization. Therefore, we postulated that submucosal fibroblasts are also involved in the innate antiviral response to HRV infection in asthma. We found that regardless of subject group, bronchial fibroblasts were highly susceptible to RV1b infection. IL-8 and IL-6 were rapidly induced by either HRV or UV-irradiated virus, suggesting that these responses did not require viral replication. In contrast, RANTES expression was dependent on viral replication. Regardless of disease status, fibroblasts did not respond to HRV infection with significant induction of IFN-\u03b2, even though both groups responded to synthetic dsRNA with similar levels of IFN-\u03b2 expression. Exogenous IFN-\u03b2 was highly protective against viral replication. Our data suggest that fibroblasts respond to HRV with a vigorous proinflammatory response but minimal IFN-\u03b2 expression. Their susceptibility to infection may cause them to be a reservoir for HRV replication in the lower airways, especially in asthmatic subjects where there is reduced protection offered by epithelial-derived IFNs. Their ability to support viral replication coupled with their vigorous proinflammatory response following infection may contribute to asthma exacerbations.<\/jats:p>","DOI":"10.4049\/jimmunol.0802471","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T20:01:20Z","timestamp":1236283280000},"page":"3660-3667","source":"Crossref","is-referenced-by-count":29,"title":["Contribution of Bronchial Fibroblasts to the Antiviral Response in Asthma"],"prefix":"10.1093","volume":"182","author":[{"given":"Nicole","family":"Bedke","sequence":"first","affiliation":[{"name":"Allergy and Inflammation Research, Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Michael","family":"Haitchi","sequence":"additional","affiliation":[{"name":"Allergy and Inflammation Research, Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Xatzipsalti","sequence":"additional","affiliation":[{"name":"Allergy and Inflammation Research, Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen T","family":"Holgate","sequence":"additional","affiliation":[{"name":"Allergy and Inflammation Research, Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna E","family":"Davies","sequence":"additional","affiliation":[{"name":"Allergy and Inflammation Research, Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,3,15]]},"reference":[{"key":"2026012807050957100_R1","first-page":"1225","article-title":"Community study of role of viral infections in exacerbations of asthma in 9\u201311 year old children.","volume-title":"Br. Med. J.","year":"1995"},{"key":"2026012807050957100_R2","first-page":"831","article-title":"Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study.","volume-title":"Lancet","year":"2002"},{"key":"2026012807050957100_R3","first-page":"295","article-title":"Respiratory viral infections drive chemokine expression and exacerbate the asthmatic response.","volume-title":"J. Allergy Clin. Immunol.","year":"2006"},{"key":"2026012807050957100_R4","first-page":"586","article-title":"IFN-\u03b3-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations.","volume-title":"J. Allergy Clin. Immunol.","year":"2007"},{"key":"2026012807050957100_R5","first-page":"879","article-title":"Type 1 interferons and the virus-host relationship: a lesson in detente.","volume-title":"Science","year":"2006"},{"key":"2026012807050957100_R6","first-page":"937","article-title":"Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012807050957100_R7","first-page":"1023","article-title":"Role of deficient type III interferon-\u03bb production in asthma exacerbations.","volume-title":"Nat. Med.","year":"2006"},{"key":"2026012807050957100_R8","first-page":"207","article-title":"Detection of rhinovirus infection of the nasal mucosa by oligonucleotide in situ hybridization.","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"1994"},{"key":"2026012807050957100_R9","first-page":"1875","article-title":"Rhinoviruses infect the lower airways.","volume-title":"J. Infect. Dis.","year":"2000"},{"key":"2026012807050957100_R10","first-page":"608","article-title":"Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor.","volume-title":"J. Med. Virol.","year":"2005"},{"key":"2026012807050957100_R11","first-page":"215","article-title":"Airway remodelling in asthma \u2014 new insights.","volume-title":"J. Allergy Clin. Immunol.","year":"2003"},{"key":"2026012807050957100_R12","first-page":"655","article-title":"The attenuated fibroblast sheath of the respiratory tract epithelial-mesenchymal trophic unit.","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"2000"},{"key":"2026012807050957100_R13","first-page":"199","article-title":"Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation.","volume-title":"Trends Immunol.","year":"2001"},{"key":"2026012807050957100_R14","first-page":"385","article-title":"The contribution of interleukin (IL)-4 and IL-13 to the epithelial- mesenchymal trophic unit in asthma.","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"2001"},{"key":"2026012807050957100_R15","first-page":"9707","article-title":"Rhinovirus infection induces expression of its own receptor intercellular adhesion molecule 1 (ICAM-1) via increased NF-\u03baB-mediated transcription.","volume-title":"J. Biol. Chem.","year":"1999"},{"key":"2026012807050957100_R16","first-page":"313","article-title":"Enhanced upregulation of smooth muscle related transcripts by TGF \u03b22 in asthmatic (myo) fibroblasts.","volume-title":"Thorax","year":"2006"},{"key":"2026012807050957100_R17","first-page":"36952","article-title":"Phosphatidylinositol 3-kinase is required for rhinovirus-induced airway epithelial cell interleukin-8 expression.","volume-title":"J. Biol. Chem.","year":"2005"},{"key":"2026012807050957100_R18","first-page":"202","article-title":"Demonstration of dual rhinovirus infection in humans by isolation of different serotypes in human heteroploid (HeLa) and human diploid fibroblast cell cultures.","volume-title":"J. Clin. Microbiol.","year":"1977"},{"key":"2026012807050957100_R19","first-page":"39","article-title":"Modulation of human lung fibroblast functions by ciclesonide: evidence for its conversion into the active metabolite desisobutyryl-ciclesonide.","volume-title":"Immunol. Lett.","year":"2007"},{"key":"2026012807050957100_R20","first-page":"71","article-title":"Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection.","volume-title":"Respir. Res.","year":"2006"},{"key":"2026012807050957100_R21","first-page":"A479","article-title":"Epithelial-mesenchymal communication following rhinovirus infection of asthmatic bronchial epithelial cells.","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2007"},{"key":"2026012807050957100_R22","first-page":"1186","article-title":"Rhinovirus activates interleukin-8 expression via a Src\/p110\u03b2 phosphatidylinositol 3-kinase\/Akt pathway in human airway epithelial cells.","volume-title":"J. Virol.","year":"2007"},{"key":"2026012807050957100_R23","first-page":"1885","article-title":"Rhinovirus-induced oxidative stress and interleukin-8 elaboration involves p47-phox but is independent of attachment to intercellular adhesion molecule-1 and viral replication.","volume-title":"J. Infect. Dis.","year":"2000"},{"key":"2026012807050957100_R24","first-page":"137","article-title":"Antiviral signaling through pattern recognition receptors.","volume-title":"J. Biochem.","year":"2007"},{"key":"2026012807050957100_R25","first-page":"731","article-title":"Double-stranded RNA induces the synthesis of specific chemokines by bronchial epithelial cells.","volume-title":"Am. J Respir. Cell Mol. Biol.","year":"2003"},{"key":"2026012807050957100_R26","first-page":"399","article-title":"Attenuation of the type I interferon response in cells infected with human rhinovirus.","volume-title":"Virology","year":"2008"},{"key":"2026012807050957100_R27","first-page":"1049","article-title":"Synthetic double-stranded RNA induces multiple genes related to inflammation through Toll-like receptor 3 depending on NF-\u03baB and\/or IRF-3 in airway epithelial cells.","volume-title":"Clin. Exp. Allergy","year":"2006"},{"key":"2026012807050957100_R28","first-page":"1364","article-title":"Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling.","volume-title":"Biochem. Biophys. Res. Commun.","year":"2002"},{"key":"2026012807050957100_R29","first-page":"793","article-title":"Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms.","volume-title":"Eur. Respir. J.","year":"2007"},{"key":"2026012807050957100_R30","first-page":"1362","article-title":"Involvement of the epidermal growth factor receptor in epithelial repair in asthma.","volume-title":"FASEB J.","year":"2000"},{"key":"2026012807050957100_R31","first-page":"499","article-title":"The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects.","volume-title":"Thorax","year":"1992"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/6\/3660\/62723273\/8699.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/6\/3660\/62723273\/8699.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:05:39Z","timestamp":1769601939000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/6\/3660\/8007744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2009,3,15]]},"published-print":{"date-parts":[[2009,3,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0802471","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,3]]},"published":{"date-parts":[[2009,3]]}}}