title: Burkholderia cenocepacia ET12 strain activates TNFR1 signalling in cystic fibrosis airway epithelial cells.
abstract: Burkholderia cenocepacia is an important pulmonary pathogen in individuals with cystic fibrosis (CF). Infection is often associated with severe pulmonary inflammation, and some patients develop a fatal necrotizing pneumonia and sepsis ('cepacia syndrome'). The mechanisms by which this species causes severe pulmonary inflammation are poorly understood. Here, we demonstrate that B. cenocepacia BC7, a potentially virulent representative of the epidemic ET12 lineage, binds to tumour necrosis factor receptor 1 (TNFR1) and activates TNFR1-related signalling pathway similar to TNF-alpha, a natural ligand for TNFR1. This interaction participates in stimulating a robust IL-8 production from CF airway epithelial cells. In contrast, BC45, a less virulent ET12 representative, and ATCC 25416, an environmental B. cepacia strain, do not bind to TNFR1 and stimulate only minimal IL-8 production from CF cells. Further, TNFR1 expression is increased in CF airway epithelial cells compared with non-CF cells. We also show that B. cenocepacia ET12 strain colocaizes with TNFR1 in vitro and in the lungs of CF patients who died due to infection with B. cenocepacia, ET12 strain. Together, these results suggest that interaction of B. cenocepacia, ET12 strain with TNFR1 may contribute to robust inflammatory responses elicited by this organism.
authors: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA. usajjan@umich.edu
authors: Umadevi S
authors: US
authors: Sajjan
authors: Marc B
authors: MB
authors: Hershenson
authors: Janet F
authors: JF
authors: Forstner
authors: John J
authors: JJ
authors: LiPuma
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D019121:Burkholderia Infections / Q000473:pathology; D042602:Burkholderia cepacia complex / Q000502:physiology*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000150:complications; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000382:microbiology
chemical_list: D016209:Interleukin-8; D047888:Receptors, Tumor Necrosis Factor, Type I
references: Science. 1989 Sep 8;245(4922):1059-65
references: 2772657
references: Am J Respir Crit Care Med. 2004 Jul 1;170(1):70-7
references: 15044201
references: Am J Respir Cell Mol Biol. 1991 Apr;4(4):313-9
references: 1849726
references: J Clin Invest. 1992 Feb;89(2):648-56
references: 1371125
references: Cell. 1993 May 7;73(3):457-67
references: 8387893
references: J Immunol. 2004 Aug 1;173(3):2031-40
references: 15265938
references: Nat Med. 2004 Aug;10(8):842-8
references: 15247912
references: Infect Immun. 2004 Sep;72(9):5126-34
references: 15322006
references: Cell. 1982 Nov;31(1):11-24
references: 6186379
references: J Pediatr. 1984 Feb;104(2):206-10
references: 6420530
references: Differentiation. 1985;30(2):130-40
references: 2420672
references: Infect Immun. 1993 Aug;61(8):3157-63
references: 7687582
references: Cell. 1995 May 19;81(4):513-23
references: 7538908
references: FEMS Immunol Med Microbiol. 1995 Apr;11(2):99-106
references: 7640678
references: Cell. 1996 Jan 26;84(2):299-308
references: 8565075
references: Immunity. 1996 Apr;4(4):387-96
references: 8612133
references: Infect Immun. 1997 Feb;65(2):617-22
references: 9009321
references: Infect Immun. 1998 Jun;66(6):2960-8
references: 9596773
references: Am J Respir Cell Mol Biol. 1998 Aug;19(2):269-77
references: 9698599
references: Infect Immun. 1999 Mar;67(3):1505-7
references: 10024601
references: Immunology. 2005 May;115(1):1-20
references: 15819693
references: J Immunol. 2005 Aug 1;175(3):1930-6
references: 16034137
references: FASEB J. 2006 Oct;20(12):2121-3
references: 16914605
references: EMBO J. 2007 Feb 7;26(3):701-9
references: 17255933
references: Infect Immun. 2000 Apr;68(4):1787-95
references: 10722565
references: J Med Microbiol. 2000 Oct;49(10):875-85
references: 11023184
references: Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L493-502
references: 11159033
references: J Med Microbiol. 2001 Jun;50(6):535-46
references: 11393291
references: Infect Immun. 2001 Aug;69(8):5138-50
references: 11447196
references: Trends Cell Biol. 2001 Sep;11(9):372-7
references: 11514191
references: Mol Med. 2001 Aug;7(8):523-34
references: 11591888
references: Lancet. 2001 Nov 24;358(9295):1780-1
references: 11734238
references: Thorax. 2002 Feb;57(2):142-5
references: 11828044
references: Cell Microbiol. 2002 Feb;4(2):73-86
references: 11896764
references: Pediatr Res. 2003 Sep;54(3):297-305
references: 12761358
references: FEMS Immunol Med Microbiol. 2003 Oct 15;38(3):273-82
references: 14522463
references: J Immunol. 2004 Feb 15;172(4):2511-21
references: 14764724
references: Eur Respir J. 2004 Feb;23(2):327-33
references: 14979512
references: Am J Respir Cell Mol Biol. 2004 May;30(5):627-34
references: 14607814
references: J Clin Invest. 2004 May;113(10):1482-9
references: 15146246
references: Thorax. 2004 Jun;59(6):526-8
references: 15170040
references: Infect Immun. 2004 Jul;72(7):4188-99
references: 15213163
references: Science. 1989 Sep 8;245(4922):1066-73
references: 2475911