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Publication : FcgammaRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis.

First Author  Clatworthy MR Year  2004
Journal  J Exp Med Volume  199
Issue  5 Pages  717-23
PubMed ID  14981111 Mgi Jnum  J:124296
Mgi Id  MGI:3721221 Doi  10.1084/jem.20032197
Citation  Clatworthy MR, et al. (2004) FcgammaRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. J Exp Med 199(5):717-23
abstractText  The immune response to infection must be controlled to ensure it is optimal for defense while avoiding the consequences of excessive inflammation, which include fatal septic shock. Mice deficient in FcgammaRIIb, an inhibitory immunoglobulin G Fc receptor, have enhanced immune responses. Therefore, we examined whether FcgammaRIIb controls the response to Streptococcus pneumoniae. Macrophages from FcgammaRIIb-deficient mice showed increased antibody-dependent phagocytosis of pneumococci in vitro, and consistent with this infected FcgammaRIIb-deficient mice demonstrated increased bacterial clearance and survival. In contrast, previously immunized FcgammaRIIb-deficient mice challenged with large inocula showed reduced survival. This correlated with increased production of the sepsis-associated cytokines tumor necrosis factor alpha and interleukin 6. We propose that FcgammaRIIb controls the balance between efficient pathogen clearance and the cytokine-mediated consequences of sepsis, with potential therapeutic implications.
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