Neurodegeneration in models of Gram-positive bacterial infections of the central nervous system

Biochem Soc Trans. 2007 Nov;35(Pt 5):1166-7. doi: 10.1042/BST0351166.

Abstract

Gram-positive bacterial infections of the central nervous system, such as meningitis, induce an extensive inflammatory response, which in turn may damage neurons. LTA (lipoteichoic acid) is a component of the Gram-positive bacterial cell wall that induces glial inflammatory activation in vitro and in vivo. It does so by binding to Toll-like receptor-2 on microglia and astrocytes, rapidly activating ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38 MAPKs (mitogen-activated protein kinases), causing NF-kappaB (nuclear factor kappaB) activation and leading to the production of pro-inflammatory cytokines and expression of inducible nitric oxide synthase (in synergy with muramyl dipeptide). LTA-activated microglia kill co-cultured neurons apparently via nitric oxide, superoxide and peroxynitrite, which may induce apoptosis of neurons that are then phagocytosed by microglia.

Publication types

  • Review

MeSH terms

  • Central Nervous System Infections / immunology
  • Central Nervous System Infections / microbiology
  • Central Nervous System Infections / pathology*
  • Gram-Positive Bacterial Infections / immunology
  • Gram-Positive Bacterial Infections / microbiology
  • Gram-Positive Bacterial Infections / pathology*
  • Humans
  • Immunity, Innate
  • Models, Biological*