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Publication : Cutting edge: MyD88 controls phagocyte NADPH oxidase function and killing of gram-negative bacteria.

First Author  Laroux FS Year  2005
Journal  J Immunol Volume  175
Issue  9 Pages  5596-600
PubMed ID  16237045 Mgi Jnum  J:119372
Mgi Id  MGI:3701913 Doi  10.4049/jimmunol.175.9.5596
Citation  Laroux FS, et al. (2005) Cutting edge: MyD88 controls phagocyte NADPH oxidase function and killing of gram-negative bacteria. J Immunol 175(9):5596-600
abstractText  MyD88 is an adaptor protein for the TLR family of proteins that has been implicated as a critical mediator of innate immune responses to pathogen detection. In this study, we report that MyD88 plays a crucial role in killing Gram-negative bacteria by primary macrophages via influencing NADPH oxidase function. Peritoneal macrophages from MyD88-/- mice exhibited a marked inability to kill Escherichia coli (F18) or an attenuated strain of Salmonella typhimurium (sseB) in vitro. This defect in killing was due to diminished NADPH oxidase-mediated production of superoxide anion in response to bacteria by MyD88-/- phagocytes as a consequence of defective NADPH oxidase assembly. Defective oxidase assembly in MyD88-deficient macrophages resulted from impaired p38 MAPK activation and subsequent phosphorylation of p47phox. Together these data demonstrate a pivotal role for MyD88 in killing Gram-negative bacteria via modulation of NADPH oxidase activity in phagocytic cells.
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