Burkholderia cenocepacia ET12 strain activates TNFR1 signalling in cystic fibrosis airway epithelial cells.
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.
Sajjan
Umadevi S
US
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA. usajjan@umich.edu
Hershenson
Marc B
MB
Forstner
Janet F
JF
LiPuma
John J
JJ
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
D016209:Interleukin-8; D047888:Receptors, Tumor Necrosis Factor, Type I
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