Bid regulates the immunological profile of murine microglia and macrophages

Glia. 2011 Mar;59(3):397-412. doi: 10.1002/glia.21109. Epub 2010 Dec 6.


Apoptosis is a controlled cell-death process mediated inter alia by proteins of the Bcl-2 family. Some proteins previously shown to promote the apoptotic process were found to have nonapoptotic functions as well. Microglia, the resident immune cells of the central nervous system, respond to brain derangements by becoming activated to contend with the brain damage. Activated microglia can also undergo activation-induced cell death. Previous studies have addressed the role of core apoptotic proteins in the death process, but whether these proteins also play a role or not in the activation process is not been reported. Here we explore the effect of the BH3-only protein Bid on the immunological features of microglia and macrophages. Our results showed that Bid regulates both the phagocytotic activities and the inflammatory profiles of these cells. Deficiency of Bid attenuated the phagocytotic activity of primary microglia and peritoneal macrophages. It also changed the expression profile of distinct inflammation-related genes in lipopolysaccharide-activated microglia and peritoneal macrophages in vitro and in an in vivo sepsis-like paradigm. Notably, similar changes followed downregulation of Bid in the N9 microglial cell line. Cell death could not be detected in any of the systems examined. Our findings demonstrate that Bid can regulate the immunological profiles of activated microglial and macrophages, via a novel nonapoptotic activity. In view of the critical role of these cells in various pathologies, including acute and chronic brain insults, our findings suggest that impairments in Bid expression may contribute to these pathologies also via a nonapoptotic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • BH3 Interacting Domain Death Agonist Protein / antagonists & inhibitors
  • BH3 Interacting Domain Death Agonist Protein / genetics
  • BH3 Interacting Domain Death Agonist Protein / physiology*
  • Cell Line
  • Cells, Cultured
  • Female
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Lipopolysaccharides / toxicity
  • Macrophages / immunology*
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / immunology*
  • Microglia / pathology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / immunology*
  • Nerve Degeneration / pathology
  • Phagocytosis / immunology
  • Signal Transduction / immunology


  • BH3 Interacting Domain Death Agonist Protein
  • Bid protein, mouse
  • Inflammation Mediators
  • Lipopolysaccharides