Neurodegeneration in models of Gram-positive bacterial infections of the central nervous system.
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.
Neher
J J
JJ
Department of Biochemistry, University of Cambridge, Downing Site, Tennis Court Road, Cambridge CB2 1QW, U.K. jjn24@cam.ac.uk
Brown
G C
GC
D002494:Central Nervous System Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007113:Immunity, Innate; D008954:Models, Biological