{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:52:42Z","timestamp":1791024762924,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,9,3]],"date-time":"2009-09-03T00:00:00Z","timestamp":1251936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\n\t\t\t\t\t<\/jats:bold> Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma.<\/jats:p><jats:p><jats:bold>Objective\n\t\t\t\t\t<\/jats:bold> Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial\u2010associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent.<\/jats:p><jats:p><jats:bold>Methods\n\t\t\t\t\t<\/jats:bold> BALB\/c mice were sensitized by intranasal administration of endotoxin<jats:sup>low<\/jats:sup> ovalbumin (OVA) in the absence or presence of viral single\u2010stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24\u2003h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end\u2010points (bronchoalveolar lavage cytology, histology, antigen\u2010specific T and B cell responses) determined at 7 weeks of age.<\/jats:p><jats:p><jats:bold>Results\n\t\t\t\t\t<\/jats:bold> Inhalational sensitization (&lt;24\u2003h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA\u2010specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxin<jats:sup>low<\/jats:sup> OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen\u2010specific production of IL\u201013 as compared with mice exposed only to endotoxin<jats:sup>low<\/jats:sup> OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA\u2010induced allergic inflammation in mice sensitized as weanlings.<\/jats:p><jats:p><jats:bold>Conclusions\n\t\t\t\t\t<\/jats:bold> Recognition of distinct microbial\u2010associated patterns in early life may preferentially promote the <jats:italic>de novo<\/jats:italic> differentiation of bystander, antigen\u2010specific CD4<jats:sup>+<\/jats:sup> T cells toward a Th2 phenotype, and promote an asthma\u2010like phenotype upon cognate antigen exposure in later life.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2009.03335.x","type":"journal-article","created":{"date-parts":[[2009,9,4]],"date-time":"2009-09-04T03:34:00Z","timestamp":1252035240000},"page":"1920-1928","source":"Crossref","is-referenced-by-count":14,"title":["Allergic sensitization is enhanced in early life through toll\u2010like receptor 7 activation"],"prefix":"10.1111","volume":"39","author":[{"given":"S.","family":"Phipps","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Hansbro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. E.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Y.","family":"Foo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. I.","family":"Matthaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. S.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.3.775"},{"key":"e_1_2_6_3_2","first-page":"528","article-title":"The immunopathology of extrinsic (atopic) and intrinsic (non\u2010atopic) asthma","volume":"20","author":"Humbert M","year":"1999","journal-title":"more similarities than differences"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/286264a0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1683"},{"key":"e_1_2_6_6_2","first-page":"1422","article-title":"Effect of an interleukin\u20104 variant on late phase asthmatic response to allergen challenge in asthmatic patients","volume":"370","author":"Wenzel S","year":"2007","journal-title":"results of two phase 2a studies"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021340"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.5.9906076"},{"key":"e_1_2_6_9_2","first-page":"500","article-title":"Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis","volume":"95","author":"Sigurs N","year":"1995","journal-title":"a prospective cohort study with matched controls"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.3484"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(98)70012-0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119516"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093620"},{"key":"e_1_2_6_14_2","first-page":"1271","article-title":"Interactions between RSV infection, asthma, and atopy","volume":"196","author":"Holt PG","year":"2002","journal-title":"unraveling the complexities"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020943"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1995.15.633"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800152105"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.7.3914"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-071340"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1660"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3107127"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1223"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/80833"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.299.6710.1259"},{"key":"e_1_2_6_25_2","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.4049\/jimmunol.163.5.2592","article-title":"Intranasal exposure to protein antigen induces immunological tolerance mediated by functionally disabled CD4+ T cells","volume":"163","author":"Tsitoura DC","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_6_26_2","first-page":"97","article-title":"Suppression of IgE responses by antigen inhalation","volume":"60","author":"Holt PG","year":"1987","journal-title":"studies on the role of genetic and environmental factors"},{"key":"e_1_2_6_27_2","first-page":"21","article-title":"Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants","volume":"21","author":"Eisenbarth SC","year":"2008","journal-title":"Nature"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/61.1.13"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200804-579OC"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.094128"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7805"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00440.2005"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.03069.x"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.2141"},{"key":"e_1_2_6_35_2","first-page":"1","article-title":"Delayed maturation of an IL\u201012\u2010producing dendritic cell subset explains the early Th2 bias in neonatal immunity","volume":"1","author":"Lee HH","year":"2008","journal-title":"J Exp Med"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2003.10.007"},{"key":"e_1_2_6_37_2","first-page":"2739","article-title":"Cutting edge","volume":"172","author":"Redecke V","year":"2004","journal-title":"activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.12.011"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.06.024"},{"key":"e_1_2_6_40_2","first-page":"303","article-title":"Interactions between influenza and bacterial respiratory pathogens","volume":"6","author":"Brundage JF.","year":"2006","journal-title":"implications for pandemic preparedness"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1765"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070891"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2222.2009.03335.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2222.2009.03335.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T03:51:39Z","timestamp":1697428299000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2222.2009.03335.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,13]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1111\/j.1365-2222.2009.03335.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2222.2009.03335.x","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,13]]}}}