{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:42:14Z","timestamp":1790390534431,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,15]],"date-time":"2018-04-15T00:00:00Z","timestamp":1523750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Eosinophils in the nasal mucosa are an elemental feature of allergic rhinitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our objective was to explore eosinophilic inflammation and its impact on respiratory virus infection at the nasal mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inflammation in the nasal mucosae of mice was evaluated in response to repetitive stimulation with strict intranasal volumes of a filtrate of <jats:italic>Alternaria alternata<\/jats:italic>. Mice were then challenged with influenza virus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Repetitive stimulation with <jats:italic>A.\u00a0alternata<\/jats:italic> resulted in eosinophil recruitment to the nasal passages in association with elevated levels of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 and eotaxin\u20101; eosinophil recruitment was diminished in <jats:italic>eotaxin\u20101<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, and abolished in <jats:italic>Rag1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. <jats:italic>A.\u00a0alternata<\/jats:italic> also resulted in elevated levels of nasal wash IgA in both wild\u2010type and eosinophil\u2010deficient <jats:italic>\u2206dbl<\/jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content> mice. Interestingly, <jats:italic>A.\u00a0alternata<\/jats:italic>\u2010treated mice responded to an influenza virus infection with profound weight loss and mortality compared to mice that received diluent alone (0% vs 100% survival, ***<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>.001); the lethal response was blunted when <jats:italic>A.\u00a0alternata<\/jats:italic> was heat\u2010inactivated. Minimal differences in virus titre were detected, and eosinophils present in the nasal passages at the time of virus inoculation provided no protection against the lethal sequelae. Interestingly, nasal wash fluids from mice treated with <jats:italic>A.\u00a0alternata<\/jats:italic> included more neutrophils and higher levels of pro\u2010inflammatory mediators in response to virus challenge, among these, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, a biomarker for disease severity in human influenza.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>Repetitive administration of <jats:italic>A.\u00a0alternata<\/jats:italic> resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. As increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be used for further exploration of these observations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13123","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T13:46:42Z","timestamp":1519393602000},"page":"691-702","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>Alternaria alternata<\/i> challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection"],"prefix":"10.1111","volume":"48","author":[{"given":"M.","family":"Ma","sequence":"first","affiliation":[{"name":"Inflammation Immunobiology Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"Redes","sequence":"additional","affiliation":[{"name":"Molecular Signal Transduction Sections Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Percopo","sequence":"additional","affiliation":[{"name":"Inflammation Immunobiology Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. M.","family":"Druey","sequence":"additional","affiliation":[{"name":"Molecular Signal Transduction Sections Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-365X","authenticated-orcid":false,"given":"H. F.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Inflammation Immunobiology Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3341"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2014.04.002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.95"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12549"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2010.03484.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3RI0314-129R"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.04.005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.6.9805083"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12716"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-016-0661-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009124"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-15-63"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.10.1465"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-071340"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-502443"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600787"},{"key":"e_1_2_8_18_1","first-page":"275","article-title":"Persistence of viral antigen in the nasal epithelium in complicated influenza","volume":"99","author":"Ebisawa IT","year":"1968","journal-title":"Am Rev Respir Dis"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01623-05"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00173.2001"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035114"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4100"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.130048"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.12.1164"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-014-8447-6"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.09.110"},{"key":"e_1_2_8_27_1","first-page":"e50490","article-title":"Characterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae","volume":"83","author":"Puchta A","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339402200402"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.07.025"},{"key":"e_1_2_8_30_1","first-page":"355","article-title":"Assays for detection of RNase A superfamily ribonucleases","volume":"160","author":"Rosenberg HF","year":"2001","journal-title":"Methods Mol Biol"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.04.010"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1016-8_22"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001751"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.080071397"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-200246"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.790117.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00359.2010"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.02.002"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.254649"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/879080"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0636-y"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356341"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102832"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2016.01.003"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(94)90107-4"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12695"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1045"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201309-1616OC"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.2"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201243018"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-016-0558-0"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2013.34.3686"},{"key":"e_1_2_8_53_1","first-page":"99","article-title":"Virus\u2010provoked rhinitis in patients who have allergies","volume":"23","author":"Fireman P","year":"2002","journal-title":"Allergy Asthma Proc"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)62263-6"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.13123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T11:57:53Z","timestamp":1694951873000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.13123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,15]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/cea.13123"],"URL":"https:\/\/doi.org\/10.1111\/cea.13123","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,15]]},"assertion":[{"value":"2017-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}