title: Burkholderia cenocepacia O polysaccharide chain contributes to caspase-1-dependent IL-1beta production in macrophages.
abstract: Burkholderia cenocepacia infections in CF patients involve heightened inflammation, fatal sepsis, and high antibiotic resistance. Proinflammatory IL-1β secretion is important in airway inflammation and tissue damage. However, little is known about this pathway in macrophages upon B. cenocepacia infection. We report here that murine macrophages infected with B. cenocepacia K56-2 produce proinflammatory cytokine IL-1β in a TLR4 and caspase-1-mediated manner. We also determined that the OPS (O antigen) of B. cenocepacia LPS contributes to IL-1β production and pyroptotic cell death. Furthermore, we showed that the malfunction of the CFTR channel augmented IL-1β production upon B. cenocepacia infection of murine macrophages. Taken together, we identified eukaryotic and bacterial factors that contribute to inflammation during B. cenocepacia infection, which may aid in the design of novel approaches to control pulmonary inflammation.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Center for Microbial Interface Biology and the Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Kotrange
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kopp
authors.forename: Anwari
authors.initials: A
authors.lastname: Akhter
authors.forename: Dalia
authors.initials: D
authors.lastname: Abdelaziz
authors.forename: Arwa
authors.initials: A
authors.lastname: Abu Khweek
authors.forename: Kyle
authors.initials: K
authors.lastname: Caution
authors.forename: Basant
authors.initials: B
authors.lastname: Abdulrahman
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.forename: Karen
authors.initials: K
authors.lastname: McCoy
authors.forename: Clay
authors.initials: C
authors.lastname: Marsh
authors.forename: Slade A
authors.initials: SA
authors.lastname: Loutet
authors.forename: Ximena
authors.initials: X
authors.lastname: Ortega
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valvano
authors.forename: Amal O
authors.initials: AO
authors.lastname: Amer
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D019121:Burkholderia Infections / Q000276:immunology / Q000382:microbiology; D057508:Burkholderia cenocepacia / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism*; D016923:Cell Death; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D019081:O Antigens / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D020170:Caspase 1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D019081:O Antigens; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse