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-κB (nuclear factor κB) 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.
Conference Article| October 25 2007
Neurodegeneration in models of Gram-positive bacterial infections of the central nervous system
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J.J. Neher, G.C. Brown; Neurodegeneration in models of Gram-positive bacterial infections of the central nervous system. Biochem Soc Trans 1 November 2007; 35 (5): 1166–1167. doi: https://doi.org/10.1042/BST0351166
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