title: Toll-like receptor 2 signaling in response to brain injury: an innate bridge to neuroinflammation.
abstract: Reactive gliosis is a prominent feature of neurodegenerative and neuroinflammatory disease in the CNS, yet the stimuli that drive this response are not known. There is growing appreciation that signaling through Toll-like receptors (TLRs), which is key to generating innate responses to infection, may have pathogen-independent roles. We show that TLR2 was selectively upregulated by microglia in the denervated zones of the hippocampus in response to stereotactic transection of axons in the entorhinal cortex. In mice lacking TLR2, there were transient, selective reductions in lesion-induced expression of cytokines and chemokines. Recruitment of T cells, but not macrophages, was delayed in TLR2-deficient mice, as well as in mice lacking TNFR1 (tumor necrosis factor receptor 1). TLR2 deficiency also affected microglial proliferative expansion, whereas all of these events were unaffected in TLR4-mutant mice. Consistent with the fact that responses in knock-out mice had all returned to wild-type levels by 8 d, there was no evidence for effects on neuronal plasticity at 20 d. These results identify a role for TLR2 signaling in the early glial response to brain injury, acting as an innate bridge to neuroinflammation.
authors.affiliation: Medical Biotechnology Center, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Babcock
authors.forename: Martin
authors.initials: M
authors.lastname: Wirenfeldt
authors.forename: Thomas
authors.initials: T
authors.lastname: Holm
authors.forename: Helle H
authors.initials: HH
authors.lastname: Nielsen
authors.forename: Lasse
authors.initials: L
authors.lastname: Dissing-Olesen
authors.forename: Henrik
authors.initials: H
authors.lastname: Toft-Hansen
authors.forename: Jason M
authors.initials: JM
authors.lastname: Millward
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D051195:Toll-Like Receptor 2