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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Vesicular Transport / metabolism
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Animals
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Burkholderia Infections / immunology
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Burkholderia Infections / microbiology
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Burkholderia cenocepacia / immunology*
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Caspase 1 / metabolism*
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Cell Death
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Cystic Fibrosis Transmembrane Conductance Regulator / genetics
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Gene Expression Regulation
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Interleukin-1beta / biosynthesis*
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Interleukin-1beta / genetics
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Macrophages / cytology
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Macrophages / enzymology
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Macrophages / immunology*
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Macrophages / microbiology*
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Mice
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Mutation / genetics
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Myeloid Differentiation Factor 88 / metabolism
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O Antigens / immunology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Toll-Like Receptor 4 / metabolism
Substances
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Adaptor Proteins, Vesicular Transport
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Interleukin-1beta
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Myeloid Differentiation Factor 88
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O Antigens
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RNA, Messenger
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TICAM-1 protein, mouse
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Cystic Fibrosis Transmembrane Conductance Regulator
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Caspase 1