 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, April 1, 2002, 22(7):2478-2486
The Toll-Like Receptor TLR4 Is Necessary for Lipopolysaccharide-Induced Oligodendrocyte Injury in the CNS
Seija Lehnardt1, *, Christian Lachance1, *, Silvia Patrizi1, *, Sharon Lefebvre1, Pamela L. Follett2, Frances E. Jensen2, Paul A. Rosenberg2, Joseph J. Volpe2, and Timothy Vartanian1 1 Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, 2 Department of Neurology, Children's Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115
The immediate or innate immune response is the first line of defense against diverse microbial pathogens and requires the expression of recently discovered toll-like receptors (TLRs). TLR4 serves as a specific receptor for lipopolysaccharide (LPS) and is localized on the surface of a subset of mammalian cells. Although innate immunity is a necessary host defense against microbial pathogens, the consequences of its activation in the CNS can be deleterious, as we show here in a developing neural model. We examined the major non-neuronal cell types in the CNS for expression of TLR4 and found that microglia expressed high levels, whereas astrocytes and oligodendrocytes expressed none. Consistent with TLR4 expression solely in microglia, we show that microglia are the only CNS glial cells that bind fluorescently tagged lipopolysaccharide. Lipopolysaccharide led to extensive oligodendrocyte death in culture only under conditions in which microglia were present. To determine whether TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte death in mixed glial cultures, we studied cultures generated from mice bearing a loss-of-function mutation in the tlr4 gene. Lipopolysaccharide failed to induce oligodendrocyte death in such cultures, in contrast to the death induced in cultures from wild-type mice. Finally, stereotactic intracerebral injection of lipopolysaccharide into the developing pericallosal white matter of immature rodents resulted in loss of oligodendrocytes and hypomyelination and periventricular cysts. Our data provide a general mechanistic link between (1) lipopolysaccharide and similar microbial molecular motifs and (2) injury to oligodendrocytes and myelin as occurs in periventricular leukomalacia and multiple sclerosis.
Key words: myelination; glia; macrophage; regeneration; degeneration; demyelinating disease
* S.L., C.L., and S.P. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/2272478-09$05.00/0
This article has been cited by other articles:
O. M. Grauer, J. W. Molling, E. Bennink, L. W. J. Toonen, R. P. M. Sutmuller, S. Nierkens, and G. J. Adema
TLR Ligands in the Local Treatment of Established Intracerebral Murine Gliomas
J. Immunol., November 15, 2008; 181(10): 6720 - 6729.
[Abstract] [Full Text] [PDF]
H. J. Yoon, S.-B. Jeon, I.-H. Kim, and E. J. Park
Regulation of TLR2 Expression by Prostaglandins in Brain Glia
J. Immunol., June 15, 2008; 180(12): 8400 - 8409.
[Abstract] [Full Text] [PDF]
J. Li, E. R. Ramenaden, J. Peng, H. Koito, J. J. Volpe, and P. A. Rosenberg
Tumor Necrosis Factor {alpha} Mediates Lipopolysaccharide-Induced Microglial Toxicity to Developing Oligodendrocytes When Astrocytes Are Present
J. Neurosci., May 14, 2008; 28(20): 5321 - 5330.
[Abstract] [Full Text] [PDF]
T. Kielian, M. Md. Syed, S. Liu, N. K. Phulwani, N. Phillips, G. Wagoner, P. D. Drew, and N. Esen
The Synthetic Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses
J. Immunol., April 1, 2008; 180(7): 5004 - 5016.
[Abstract] [Full Text] [PDF]
S. Lehnardt, E. Schott, T. Trimbuch, D. Laubisch, C. Krueger, G. Wulczyn, R. Nitsch, and J. R. Weber
A Vicious Cycle Involving Release of Heat Shock Protein 60 from Injured Cells and Activation of Toll-Like Receptor 4 Mediates Neurodegeneration in the CNS
J. Neurosci., March 5, 2008; 28(10): 2320 - 2331.
[Abstract] [Full Text] [PDF]
O Khwaja and J J Volpe
Pathogenesis of cerebral white matter injury of prematurity
Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2008; 93(2): F153 - F161.
[Abstract] [Full Text] [PDF]
J. S. Cameron, L. Alexopoulou, J. A. Sloane, A. B. DiBernardo, Y. Ma, B. Kosaras, R. Flavell, S. M. Strittmatter, J. Volpe, R. Sidman, et al.
Toll-Like Receptor 3 Is a Potent Negative Regulator of Axonal Growth in Mammals
J. Neurosci., November 21, 2007; 27(47): 13033 - 13041.
[Abstract] [Full Text] [PDF]
A. Boivin, I. Pineau, B. Barrette, M. Filali, N. Vallieres, S. Rivest, and S. Lacroix
Toll-Like Receptor Signaling Is Critical for Wallerian Degeneration and Functional Recovery after Peripheral Nerve Injury
J. Neurosci., November 14, 2007; 27(46): 12565 - 12576.
[Abstract] [Full Text] [PDF]
S. Kannan, F. Saadani-Makki, O. Muzik, P. Chakraborty, T. J. Mangner, J. Janisse, R. Romero, and D. C. Chugani
Microglial Activation in Perinatal Rabbit Brain Induced by Intrauterine Inflammation: Detection with 11C-(R)-PK11195 and Small-Animal PET
J. Nucl. Med., June 1, 2007; 48(6): 946 - 954.
[Abstract] [Full Text] [PDF]
M. Domercq, M. V. Sanchez-Gomez, C. Sherwin, E. Etxebarria, R. Fern, and C. Matute
System xc- and Glutamate Transporter Inhibition Mediates Microglial Toxicity to Oligodendrocytes
J. Immunol., May 15, 2007; 178(10): 6549 - 6556.
[Abstract] [Full Text] [PDF]
T. Kielian, N. K. Phulwani, N. Esen, M. Md. Syed, A. C. Haney, K. McCastlain, and J. Johnson
MyD88-Dependent Signals Are Essential for the Host Immune Response in Experimental Brain Abscess
J. Immunol., April 1, 2007; 178(7): 4528 - 4537.
[Abstract] [Full Text] [PDF]
J. R. Caso, J. M. Pradillo, O. Hurtado, P. Lorenzo, M. A. Moro, and I. Lizasoain
Toll-Like Receptor 4 Is Involved in Brain Damage and Inflammation After Experimental Stroke
Circulation, March 27, 2007; 115(12): 1599 - 1608.
[Abstract] [Full Text] [PDF]
R. A. Adams, J. Bauer, M. J. Flick, S. L. Sikorski, T. Nuriel, H. Lassmann, J. L. Degen, and K. Akassoglou
The fibrin-derived {gamma}377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease
J. Exp. Med., March 19, 2007; 204(3): 571 - 582.
[Abstract] [Full Text] [PDF]
A. A. Babcock, M. Wirenfeldt, T. Holm, H. H. Nielsen, L. Dissing-Olesen, H. Toft-Hansen, J. M. Millward, R. Landmann, S. Rivest, B. Finsen, et al.
Toll-Like Receptor 2 Signaling in Response to Brain Injury: An Innate Bridge to Neuroinflammation
J. Neurosci., December 6, 2006; 26(49): 12826 - 12837.
[Abstract] [Full Text] [PDF]
H. Zhou, B. M. Lapointe, S. R. Clark, L. Zbytnuik, and P. Kubes
A Requirement for Microglial TLR4 in Leukocyte Recruitment into Brain in Response to Lipopolysaccharide
J. Immunol., December 1, 2006; 177(11): 8103 - 8110.
[Abstract] [Full Text] [PDF]
S. A. Back, A. Riddle, and A. R. Hohimer
Topical Review: Role of Instrumented Fetal Sheep Preparations in Defining the Pathogenesis of Human Periventricular White-Matter Injury
J Child Neurol, July 1, 2006; 21(7): 582 - 589.
[Abstract] [PDF]
S. Lehnardt, P. Henneke, E. Lien, D. L. Kasper, J. J. Volpe, I. Bechmann, R. Nitsch, J. R. Weber, D. T. Golenbock, and T. Vartanian
A Mechanism for Neurodegeneration Induced by Group B Streptococci through Activation of the TLR2/MyD88 Pathway in Microglia
J. Immunol., July 1, 2006; 177(1): 583 - 592.
[Abstract] [Full Text] [PDF]
A. Rolland, E. Jouvin-Marche, C. Viret, M. Faure, H. Perron, and P. N. Marche
The Envelope Protein of a Human Endogenous Retrovirus-W Family Activates Innate Immunity through CD14/TLR4 and Promotes Th1-Like Responses.
J. Immunol., June 15, 2006; 176(12): 7636 - 7644.
[Abstract] [Full Text] [PDF]
N. Esen and T. Kielian
Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns.
J. Immunol., June 1, 2006; 176(11): 6802 - 6811.
[Abstract] [Full Text] [PDF]
H.-J. Kim, A. B. DiBernardo, J. A. Sloane, M. N. Rasband, D. Solomon, B. Kosaras, S. P. Kwak, and T. K. Vartanian
WAVE1 Is Required for Oligodendrocyte Morphogenesis and Normal CNS Myelination
J. Neurosci., May 24, 2006; 26(21): 5849 - 5859.
[Abstract] [Full Text] [PDF]
I. Jou, J. H. Lee, S. Y. Park, H. J. Yoon, E.-H. Joe, and E. J. Park
Gangliosides Trigger Inflammatory Responses via TLR4 in Brain Glia
Am. J. Pathol., May 1, 2006; 168(5): 1619 - 1630.
[Abstract] [Full Text] [PDF]
R P Lisak, J A Benjamins, B Bealmear, B Yao, S Land, L Nedelkoska, and D Skundric
Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for immune-related molecules by central nervous system mixed glial cell cultures
Multiple Sclerosis, April 1, 2006; 12(2): 149 - 168.
[Abstract] [PDF]
R. D. Folkerth
Neuropathologic Substrate of Cerebral Palsy
J Child Neurol, December 1, 2005; 20(12): 940 - 949.
[Abstract] [PDF]
F. E. Jensen
Role of Glutamate Receptors in Periventricular Leukomalacia
J Child Neurol, December 1, 2005; 20(12): 950 - 959.
[Abstract] [PDF]
P. Svedin, I. Kjellmer, A.-K. Welin, S. Blad, and C. Mallard
Maturational Effects of Lipopolysaccharide on White-Matter Injury in Fetal Sheep
J Child Neurol, December 1, 2005; 20(12): 960 - 964.
[Abstract] [PDF]
J. Li, O. Baud, T. Vartanian, J. J. Volpe, and P. A. Rosenberg
Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes
PNAS, July 12, 2005; 102(28): 9936 - 9941.
[Abstract] [Full Text] [PDF]
C. Sherwin and R. Fern
Acute Lipopolysaccharide-Mediated Injury in Neonatal White Matter Glia: Role of TNF-{alpha}, IL-1{beta}, and Calcium
J. Immunol., July 1, 2005; 175(1): 155 - 161.
[Abstract] [Full Text] [PDF]
P. A. Felts, A.-M. Woolston, H. B. Fernando, S. Asquith, N. A. Gregson, O. J. Mizzi, and K. J. Smith
Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide
Brain, July 1, 2005; 128(7): 1649 - 1666.
[Abstract] [Full Text] [PDF]
G. Soucy, G. Boivin, F. Labrie, and S. Rivest
Estradiol Is Required for a Proper Immune Response to Bacterial and Viral Pathogens in the Female Brain
J. Immunol., May 15, 2005; 174(10): 6391 - 6398.
[Abstract] [Full Text] [PDF]
F. Y. Tanga, N. Nutile-McMenemy, and J. A. DeLeo
The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy
PNAS, April 19, 2005; 102(16): 5856 - 5861.
[Abstract] [Full Text] [PDF]
S. Chakravarty and M. Herkenham
Toll-Like Receptor 4 on Nonhematopoietic Cells Sustains CNS Inflammation during Endotoxemia, Independent of Systemic Cytokines
J. Neurosci., February 16, 2005; 25(7): 1788 - 1796.
[Abstract] [Full Text] [PDF]
I. Glezer and S. Rivest
Glucocorticoids: Protectors of the Brain during Innate Immune Responses
Neuroscientist, December 1, 2004; 10(6): 538 - 552.
[Abstract] [PDF]
M. D. Nguyen, T. D'Aigle, G. Gowing, J.-P. Julien, and S. Rivest
Exacerbation of Motor Neuron Disease by Chronic Stimulation of Innate Immunity in a Mouse Model of Amyotrophic Lateral Sclerosis
J. Neurosci., February 11, 2004; 24(6): 1340 - 1349.
[Abstract] [Full Text] [PDF]
J. A. Deleo, F. Y. Tanga, and V. L. Tawfik
Neuroimmune Activation and Neuroinflammation in Chronic Pain and Opioid Tolerance/Hyperalgesia
Neuroscientist, February 1, 2004; 10(1): 40 - 52.
[Abstract] [PDF]
J. Imitola, E. Y. Snyder, and S. J. Khoury
Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis
Physiol Genomics, August 15, 2003; 14(3): 171 - 197.
[Abstract] [Full Text] [PDF]
S. Lehnardt, L. Massillon, P. Follett, F. E. Jensen, R. Ratan, P. A. Rosenberg, J. J. Volpe, and T. Vartanian
Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
PNAS, July 8, 2003; 100(14): 8514 - 8519.
[Abstract] [Full Text] [PDF]
J. J. Volpe
Cerebral White Matter Injury of the Premature Infant--More Common Than You Think
Pediatrics, July 1, 2003; 112(1): 176 - 180.
[Full Text] [PDF]
A. Jinno-Oue, S. G. Wilt, C. Hanson, N. V. Dugger, P. M. Hoffman, M. Masuda, and S. K. Ruscetti
Expression of Inducible Nitric Oxide Synthase and Elevation of Tyrosine Nitration of a 32-Kilodalton Cellular Protein in Brain Capillary Endothelial Cells from Rats Infected with a Neuropathogenic Murine Leukemia Virus
J. Virol., May 1, 2003; 77(9): 5145 - 5151.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|