title: Immune Recognition of the Epidemic Cystic Fibrosis Pathogen Burkholderia dolosa.
abstract: Burkholderia dolosacaused an outbreak in the cystic fibrosis (CF) clinic at Boston Children's Hospital from 1998 to 2005 and led to the infection of over 40 patients, many of whom died due to complications from infection by this organism. To assess whetherB. dolosasignificantly contributes to disease or is recognized by the host immune response, mice were infected with a sequenced outbreakB. dolosastrain, AU0158, and responses were compared to those to the well-studied CF pathogenPseudomonas aeruginosaIn parallel, mice were also infected with a polar flagellin mutant ofB. dolosato examine the role of flagella inB. dolosalung colonization. The results showed a higher persistence in the host byB. dolosastrains, and yet, neutrophil recruitment and cytokine production were lower than those withP. aeruginosaThe ability of host immune cells to recognizeB. dolosawas then assessed,B. dolosainduced a robust cytokine response in cultured cells, and this effect was dependent on the flagella only when bacteria were dead. Together, these results suggest thatB. dolosacan be recognized by host cellsin vitrobut may avoid or suppress the host immune responsein vivothrough unknown mechanisms.B. dolosawas then compared to otherBurkholderiaspecies and found to induce similar levels of cytokine production despite being internalized by macrophages more thanBurkholderia cenocepaciastrains. These data suggest thatB. dolosaAU0158 may act differently with host cells and is recognized differently by immune systems than are otherBurkholderiastrains or species.
authors.affiliation: IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Service de Réanimation médico-chirurgicale, Hôpital Louis Mourier, AP-HP, Colombes, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Roux
authors.affiliation: Department of Biology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Weatherholt
authors.affiliation: Department of Biology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Clark
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gadjeva
authors.affiliation: Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Renaud
authors.affiliation: Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USA.
authors.forename: David
authors.initials: D
authors.lastname: Scott
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.|Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, and Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Channing Laboratory, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Pier
authors.affiliation: Division of Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.affiliation: Department of Biology, University of Louisville, Louisville, Kentucky, USA deborah.yoder-himes@louisville.edu.
authors.forename: Deborah R
authors.identifier: http://orcid.org/0000-0001-9576-3833
authors.initials: DR
authors.lastname: Yoder-Himes
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D019117:Burkholderia / Q000235:genetics / Q000276:immunology; D019121:Burkholderia Infections / Q000276:immunology* / Q000382:microbiology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D058872:Epidemics; D005260:Female; D005407:Flagella / Q000235:genetics / Q000276:immunology*; D005408:Flagellin / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D005408:Flagellin
keywords: Burkholderia dolosa; cytokines; flagella; immune; lung