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In the human respiratory pathogen<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bordetella pertussis<\/jats:named-content>, the causative agent of whooping cough, pertussis toxin (PT) is a key virulence factor that promotes colonization, suppresses innate immune responses during early infection, and causes systemic disease symptoms. To determine the full extent of PT-associated gene regulation in the airways through the peak of infection, we measured global transcriptional profiles in the lungs of BALB\/c mice infected with wild-type (WT) or PT-deficient (\u0394PT)<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pertussis<\/jats:named-content>. \u0394PT bacteria were inoculated at a dose equivalent to the WT dose and at a high dose (\u0394PT<jats:sup>high<\/jats:sup>) to distinguish effects caused by higher bacterial loads achieved in WT infection from effects associated with PT. The results demonstrated that PT was associated with a significant upregulation of immune and inflammatory response genes as well as several other genes implicated in airway pathology. In contrast to the early, transient responses observed for \u0394PT<jats:sup>high<\/jats:sup>infection, WT infection induced a prolonged expression of inflammatory genes and increased the extent and duration of lung histopathology. In addition, the administration of purified PT to \u0394PT<jats:sup>high<\/jats:sup>-infected mice 1 day after bacterial inoculation exacerbated and prolonged inflammatory responses and airway pathology. These data indicate that PT not only is associated with exacerbated host airway responses during peak<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pertussis<\/jats:named-content>infection but also may inhibit host mechanisms of attenuating and resolving inflammation in the airways, suggesting possible links between PT and pertussis disease symptoms.<\/jats:p>","DOI":"10.1128\/iai.00808-12","type":"journal-article","created":{"date-parts":[[2012,10,2]],"date-time":"2012-10-02T06:04:49Z","timestamp":1349157889000},"page":"4317-4332","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":68,"title":["Pertussis Toxin Exacerbates and Prolongs Airway Inflammatory Responses during Bordetella pertussis Infection"],"prefix":"10.1128","volume":"80","author":[{"given":"Carey E.","family":"Connelly","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yezhou","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H.","family":"Carbonetti","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.071"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00203-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.5.597"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00895-08"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007079"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0271OC"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-007-0227-5"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03441.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00297-2"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.07.074"},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4049\/jimmunol.159.1.497","article-title":"Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis","volume":"159","author":"Brabb T","year":"1997","unstructured":"BrabbT. 1997. 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