TLR signaling tailors innate immune responses in human microglia and astrocytes
Open accessAbstract
The specific signals mediating the activation of microglia and astrocytes as a prelude to, or consequence of, CNS inflammation continue to be defined. We investigated TLRs as novel receptors mediating innate immune responses in human glial cells. We find that microglia express mRNA for TLRs 1-9, whereas astrocytes express robust TLR3, low-level TLR 1, 4, 5, and 9, and rare-to-undetectable TLR 2, 6, 7, 8, and 10 mRNA (quantitative real-time PCR). We focused on TLRs 3 and 4, which can signal through both the MyD88-dependent and -independent pathways, and on the MyD88-restricted TLR2. By flow cytometry, we established that microglia strongly express cell surface TLR2; TLR3 is expressed at higher levels intracellularly. Astrocytes express both cell surface and intracellular TLR3. All three TLRs trigger microglial activation upon ligation. TLR3 signaling induces the strongest proinflammatory polarizing response, characterized by secretion of high levels of IL-12, TNF-alpha, IL-6, CXCL-10, and IL-10, and the expression of IFN-beta. CXCL-10 and IL-10 secretion following TLR4 ligation are comparable to that of TLR3; however, other responses were lower or absent. TLR2-mediated responses are dominated by IL-6 and IL-10 secretion. Astrocytes respond to TLR3 ligation, producing IL-6, CXCL-10, and IFN-beta, implicating these cells as contributors to proinflammatory responses. Initial TLR-mediated glial activation also regulates consequent TLR expression; while TLR2 and TLR3 are subject to positive feedback, TLR4 is down-regulated in microglia. Astrocytes up-regulate all three TLRs following TLR3 ligation. Our data indicate that activation of innate immune responses in the CNS is not homogeneous but rather tailored according to cell type and environmental signal.
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TLR4 and TLR2 are associated with both neuro-inflammation and clearance of protein aggregates in neurodegenerative disorders.
“Concretely, TLR4 and TLR2 are associated with both neuro-inflammation and clearance of protein aggregates in neurodegenerative disorders (Jack et al., 2005).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Jack et al., 2005
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Cites
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205 · see citing works
Toll-like receptor control of the adaptive immune responses
Iwasaki, A., & Medzhitov, R. M. (2004) · Nature Immunology · doi:10.1038/ni1112 · Cited by 4,166 · see citing works
Takeda, K., & Akira, S. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2003.10.003 · Cited by 2,461 · see citing works
Decoding the Patterns of Self and Nonself by the Innate Immune System
Medzhitov, R., & Janeway, C. A. (2002) · Science · doi:10.1126/science.1068883 · Cited by 2,154 · see citing works
Inferences, questions and possibilities in Toll-like receptor signalling
Beutler, B. (2004) · Nature · doi:10.1038/nature02761 · Cited by 1,458 · see citing works
Dendritic-cell control of pathogen-driven T-cell polarization
Kapsenberg, M. L. (2003) · Nature reviews. Immunology · doi:10.1038/nri1246 · Cited by 1,440 · see citing works
Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
Olson, J. K., & Miller, S. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3916 · Cited by 1,215 · see citing works
LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF
Fitzgerald, K. A., Rowe, D. C., Barnes, B. J., Caffrey, D. R., Visintin, A., Latz, E., Monks, B. G., Pitha, P. M., & Golenbock, D. T. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031023 · Cited by 1,193 · see citing works
Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion
Barnett, M. H., & Prineas, J. W. (2004) · Annals of Neurology · doi:10.1002/ana.20016 · Cited by 1,184 · see citing works
mRNA is an endogenous ligand for toll-like receptor 3
Karikó, K., Ni, H., Capodici, J., Lamphier, M., & Weissman, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310175200 · Cited by 1,062 · see citing works
Broad Expression of Toll-Like Receptors in the Human Central Nervous System
Bsibsi, M., Ravid, R., Gveric, D. O., & van Noort, J. M. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.11.1013 · Cited by 1,000 · see citing works
Subcellular Localization of Toll-Like Receptor 3 in Human Dendritic Cells
Matsumoto, M., Funami, K., Tanabe, M., Oshiumi, H., Shingai, M., Seto, Y., Yamamoto, A., & Seya, T. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.6.3154 · Cited by 708 · see citing works
Goverman, J. M., Woods, A., Larson, L., Weiner, L. P., Hood, L., & Zaller, D. M. (1993) · Cell · doi:10.1016/0092-8674(93)90074-z · Cited by 684 · see citing works
Dynamics of microglial activation: A confocal time-lapse analysis in hippocampal slices
Stence, N., Waite, M., & Dailey, M. E. (2001) · Glia · doi:10.1002/1098-1136(200103)33:3 · Cited by 617 · see citing works
Regulation of Toll-Like Receptors in Human Monocytes and Dendritic Cells
Visintin, A., Mazzoni, A., Spitzer, J. H., Wyllie, D. H., Dower, S., & Segal, D. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.1.249 · Cited by 611 · see citing works
Boonstra, A., Asselin‐Paturel, C., Gilliet, M. F., Crain, C., Trinchieri, G., Liu, Y.-J., & O’Garra, A. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021908 · Cited by 549 · see citing works
Toll-like receptor 2 as a major gene for asthma in children of European farmers
Eder, W., Klimecki, W. J., Yu, L., von Mutius, E., Riedler, J., Braun‐Fahrländer, C., Nowak, D., & Martínez, F. D. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2003.12.374 · Cited by 509 · see citing works
Dillon, S. M., Agrawal, A., Dyke, T. E. V., Landreth, G. E., McCauley, L. K., Koh, A. J., Maliszewski, C. R., Akira, S., & Pulendran, B. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.8.4733 · Cited by 460 · see citing works
Redecke, V., Häcker, H., Datta, S. K., Fermin, A., Pitha, P. M., Broide, D. H., & Raz, E. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2739 · Cited by 448 · see citing works
Molecular insights on the cerebral innate immune system
Rivest, S. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00055-7 · Cited by 417 · see citing works
Differential activation of astrocytes by innate and adaptive immune stimuli
Carpentier, P. A., Begolka, W. S., Olson, J. K., Elhofy, A., Karpus, W. J., & Miller, S. D. (2004) · Glia · doi:10.1002/glia.20117 · Cited by 359 · see citing works
Toll-like receptors and dendritic cells: for whom the bug tolls
Sousa, C. R. E. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2003.10.004 · Cited by 341 · see citing works
Of mice and men: species variations of Toll-like receptor expression
Rehli, M. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02259-7 · Cited by 323 · see citing works
Influence of infection on exacerbations of multiple sclerosis
PANITCH, H. S. (1994) · Annals of Neurology · doi:10.1002/ana.410360709 · Cited by 277 · see citing works
Preferential expression and function of Toll-like receptor 3 in human astrocytes
Farina, C., Krumbholz, M., Giese, T., Hartmann, G., Aloisi, F., & Meinl, E. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.09.009 · Cited by 256 · see citing works
Protocols for Neural Cell Culture
FEDOROFF, S., & Richardson, A. K. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90164-h · Cited by 249 · see citing works
Species-specific Regulation of Toll-like Receptor 3 Genes in Men and Mice
Heinz, S., Haehnel, V., Karaghiosoff, M., Schwarzfischer, L., Müller, M., Krause, S. W., & Rehli, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301476200 · Cited by 202 · see citing works
DSouza, S., Alinauskas, K. A., McCrea, E., Goodyer, C. G., & Antel, J. P. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-11-07293.1995 · Cited by 180 · see citing works
Adib‐Conquy, M., & Cavaillon, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200705200 · Cited by 148 · see citing works
Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis
Schrijver, I. A. (2001) · Brain · doi:10.1093/brain/124.8.1544 · Cited by 143 · see citing works
Kielian, T., Mayes, P. M., & Kielian, M. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00216-3 · Cited by 129 · see citing works
Pisegna, S., Pirozzi, G., Piccoli, M., Frati, L., Santoni, A., & Palmieri, G. (2004) · Blood · doi:10.1182/blood-2004-05-1860 · Cited by 120 · see citing works
Visser, L. H., de Heer, H. J., Boven, L. A., van Riel, D. A. J., van Meurs, M., Melief, M., Zähringer, U., van Strijp, J. A. G., Lambrecht, B. N., Nieuwenhuis, E. E. S., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.808 · Cited by 119 · see citing works
Jotwani, R., Pulendran, B., Agrawal, S., & Cutler, C. W. (2003) · European Journal of Immunology · doi:10.1002/eji.200324392 · Cited by 112 · see citing works
Relapsing-Remitting Multiple Sclerosis and Human Herpesvirus 6 Active Infection
Álvarez‐Lafuente, R., Heras, V. D. L., Bartolomé, M., Picazo, J. J., & Arroyo, R. (2004) · Archives of Neurology · doi:10.1001/archneur.61.10.1523 · Cited by 111 · see citing works
Nagai, T., Devergne, O., Mueller, T., Perkins, D. L., van Seventer, J. M., & van Seventer, G. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.10.5233 · Cited by 105 · see citing works
Lipoprotein I, a TLR2/4 Ligand Modulates Th2-Driven Allergic Immune Responses
Revets, H., PYNAERT, G. N., Grooten, J., & BAETSELIER, P. D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.1097 · Cited by 102 · see citing works
Amyloid precursor protein (APP) expression in multiple sclerosis lesions
Gehrmann, J., Banati, R. B., Cuzner, M. L., Kreutzberg, G. W., & Newcombe, J. (1995) · Glia · doi:10.1002/glia.440150206 · Cited by 96 · see citing works
Becher, B., Dodelet, V. C., Fedorowicz, V. J., & Antel, J. P. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118946 · Cited by 94 · see citing works
Astrocytes in chronic active multiple sclerosis plaques express MHC class II molecules
Zeinstra, E., Wilczak, N., Streefland, C., & Keyser, J. D. (2000) · Neuroreport · doi:10.1097/00001756-200001170-00018 · Cited by 87 · see citing works
Zeinstra, E. M. P. E., Wilczak, N., & Keyser, J. D. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00462-9 · Cited by 83 · see citing works
Culture of Glial Cells from Human Brain Biopsies
Yong, V. W., & Antel, J. P. (1997) · Humana Press eBooks · doi:10.1007/978-1-4757-2586-5_11 · Cited by 71 · see citing works
Contini, C., Cultrera, R., Seraceni, S., Castellazzi, M., Granieri, E., & Fainardi, E. (2004) · Multiple Sclerosis Journal · doi:10.1191/1352458504ms1049oa · Cited by 35 · see citing works
Carenini, S., Montag, D., Schachner, M., & Martini, R. (1999) · Glia · doi:10.1002/(sici)1098-1136(199909)27:3 · Cited by 32 · see citing works
Human brain endothelial cells supply support for monocyte immunoregulatory functions
Seguin, R. M., Moditi, Z., Rotondo, R. L., Biernacki, K., Wosik, K., Prat, A., & Antel, J. P. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00431-9 · Cited by 13 · see citing works
Zujovic (2000) · doi:10.1002/(sici)1098-1136(20000215)29:4
Flagged first, then by citations
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Sorted by citations
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,152 · see citing works
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · see citing works
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547 · see citing works
Verkhratsky, A., & Nedergaard, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00042.2016 · Cited by 1,678 · see citing works
“In human astrocytes expression of a TLR1 5 and TLR9 has been reported (250, 779); of these TLR2 4 were identified also in vivo, especially in pathological conditions (250, 779, 1695).”
Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4106 · Cited by 1,559 · see citing works
“Human fetal astrocytes were isolated as previously described 11,63 from human CNS tissue from fetuses at 17–23 weeks of gestation obtained from the Human Fetal Tissue Repository (Albert Einstein College of Medicine) following Canadian Institutes of Health Research– approved guidelines.”
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
“109 The relatively low expression of TLRs in astrocytes suggests they may have limited ability to respond directly to various pathogens.”
BackgroundAstrocytes are active players in cerebral innate immunity
Farina, C., Aloisi, F., & Meinl, E. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.01.005 · Cited by 1,304 · see citing works
TLR3 Deficiency in Patients with Herpes Simplex Encephalitis
Zhang, S., Jouanguy, E., Ugolini, S., Smahi, A., Elain, G., Romero, P. J., Segal, D. M., Sancho‐Shimizu, V., Lorenzo, L., Puel, A., et al. (2007) · Science · doi:10.1126/science.1139522 · Cited by 1,165 · see citing works
Microglial control of astrocytes in response to microbial metabolites
Rothhammer, V., Borucki, D. M., Tjon, E. C., Takenaka, M. C., Chao, C.-C., Ardura-Fabregat, A., de Lima, K. A., Gutiérrez-Vázquez, C., Hewson, P., Staszewski, O., et al. (2018) · Nature · doi:10.1038/s41586-018-0119-x · Cited by 1,051 · see citing works
Regulation of innate immune responses in the brain
Rivest, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2565 · Cited by 843 · see citing works
Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits
Tang, S., Arumugam, T. V., Xu, X. Z. S., Cheng, A., Mughal, M. R., Jo, D., Lathia, J. D., Siler, D. A., Chigurupati, S., Ouyang, X., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702553104 · Cited by 765 · see citing works
Toll-like receptors in immunity and inflammatory diseases: Past, present, and future
Kumar, V. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.03.002 · Cited by 649 · see citing works
“TLRs are either expressed extracellularly on the cell surface (For example, TLR1, TLR2, TLR4, TLR5, TLR6 , and probably TLR11 and TLR12 of mice and TLR10 of humans are expressed largely on the cell surface of innate immune cells) or intracellularly in the cytosolic compartment inside vesicles, for example in endosomes…”
Lehnardt, S. (2009) · Glia · doi:10.1002/glia.20928 · Cited by 596 · see citing works
“…signaling proteins are expressed in the CNS (Bowman et al., 2003; Bsibsi et al., 2002; Dalpke et al., 2002; Esen et al., 2004; Farina et al., 2005; Jack et al., 2005; Kielian et al., 2002; Laflamme and Rivest, 2001; Lehnardt et al., 2002, 2003; Nishimura and Naito, 2005; Olson and Miller, 2004).”
BackgroundInfluentialNeuroinflammation in the central nervous system: Symphony of glial cells
Yang, Q., & Zhou, J. (2018) · Glia · doi:10.1002/glia.23571 · Cited by 520 · see citing works
Hagberg, H., Gressèns, P., & Mallard, C. E. (2011) · Annals of Neurology · doi:10.1002/ana.22620 · Cited by 519 · see citing works
Microglia during development and aging
Harry, G. J. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.04.013 · Cited by 524 · see citing works
“This elevation in proinflammatory cytokines is accompanied by a decrease in anti-inflammatory cytokines, such as IL-10 (Ye and Johnson, 2001).”
BackgroundInfluentialRegulation of astrocyte activation by glycolipids drives chronic CNS inflammation
Mayo, L., Trauger, S. A., Blain, M., Nadeau, M., Patel, B., Alvarez, J. I., Mascanfroni, I. D., Yeste, A., Kivisäkk, P., Kallas, K., et al. (2014) · Nature Medicine · doi:10.1038/nm.3681 · Cited by 472 · see citing works
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
“Concretely, TLR4 and TLR2 are associated with both neuro-inflammation and clearance of protein aggregates in neurodegenerative disorders (Jack et al., 2005).”
BackgroundThe microglial "activation" continuum: from innate to adaptive responses
Town, T., Nikolic, V., & Tan, J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-24 · Cited by 456 · see citing works
“It has recently been shown that microglia respond to poly I:C [a synthetic doublestranded (ds) RNA analog thought to be recognized by TLR3, [39]] by producing pro-inflammatory cytokines and chemokines [40], and microglial pro-inflammatory responses to dsRNA seem to be dependent on TLR3, as TLR3-deficient microglia hav…”
Estrogens, Neuroinflammation, and Neurodegeneration
Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1007 · Cited by 423 · see citing works
Toll-Like Receptors in Neurodegeneration
Okun, E., Griffioen, K., Lathia, J., Tang, S.-C., Mattson, M., & Arumugam, T. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.09.001 · Cited by 459 · see citing works
Balancing the immune response in the brain: IL-10 and its regulation
Lobo‐Silva, D., Carriche, G. M., Castro, A. G., Roque, S., & Saraiva, M. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0763-8 · Cited by 430 · see citing works
“receptors (TLRs), which upon activation lead to the production of several inflammatory mediators [34, 35].”
BackgroundRole of Inflammation and Its Mediators in Acute Ischemic Stroke
Jin, R., Liu, L., Zhang, S., Nanda, A., & Li, G. (2013) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-013-9508-6 · Cited by 422 · see citing works
“TLRs are transmembrane proteins expressed by a variety of immune cells and brain-resident cells, such as B cells, dendritic cells, microglia, cerebral endothelium, astrocytes, oligodendrocytes, and neurons [128–131].”
BackgroundRegulation of microglial activation in stroke
Zhao, S.-C., Ma, L.-S., Chu, Z., Xu, H., Wu, W.-Q., & Liu, F. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2016.162 · Cited by 411 · see citing works
Vezzani, A., Maroso, M., Balosso, S., Sanchez, M.-A., & Bartfai, T. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.03.018 · Cited by 402 · see citing works
“…in the medium or due to cell preparation procedures which may mechanically activate them, the in vivo pattern of expression of the TLR receptors appears to be mostly restricted to TLR2, TLR3 and TLR4 both in rodents and in human tissue (Bsibsi et al., 2002; Jack et al., 2005; Okun et al., 2009).”
Parainflammation, Chronic Inflammation and Age-Related Macular Degeneration
Chen, M., & Xu, H. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri0615-239r · Cited by 381 · see citing works
“express various TLRs [81, 82] that allow them to monitor the surrounding microenvironment.”
BackgroundThe mucosal immune system: master regulator of bidirectional gut-brain communications
Powell, N., Walker, M. M., & Talley, N. J. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.191 · Cited by 379 · see citing works
Neuroinflammation and regulation of glial glutamate uptake in neurological disorders
Tilleux, S., & Hermans, E. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21325 · Cited by 381 · see citing works
“brain injuries (Bowman et al., 2003; Jack et al., 2005), data from in vivo studies suggest that early microglial activation precedes the induction of astrocyte-specific markers (Raghavendra et al.”
BackgroundInfluentialMicroglia and Inflammation in Alzheimers Disease
Mandrekar-Colucci, S., & Landreth, G. E. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791012071 · Cited by 421 · see citing works
“In the brain, TLRs are expressed mainly on microglia; however, recently it has been reported that a subset of TLRs are expressed on neurons and astrocytes [95, 96].”
BackgroundThe type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice
Guo, B., Chang, E. Y., & Cheng, G. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33342 · Cited by 372 · see citing works
“Thus, TLRs play an important role by inducing inflammatory cytokine milieu, which may promote Th17 development and contribute to the pathogenesis of autoimmune disease.”
BackgroundInfluentialRole of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases
Hsieh, H., & Yang, C. (2013) · BioMed Research International · doi:10.1155/2013/484613 · Cited by 370 · see citing works
“TLR signalings in astrocytes have been shown to be involved in inflammatory responses in CNS [80], accompanied with upregulation of genes with inflammatory and proapoptotic effects [81].”
BackgroundThe Role of Astrocytes in Multiple Sclerosis
Ponath, G. D., Park, C., & Pitt, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00217 · Cited by 356 · see citing works
Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells
Lafaille, F. G., Pessach, I. M., Zhang, S., Ciancanelli, M. J., Casadio, M., Abhyankar, A., Ying, S., Keros, S., Goldstein, P. A., Mostoslavsky, G., et al. (2012) · Nature · doi:10.1038/nature11583 · Cited by 341 · see citing works
“Hematopoietic cell-derived microglial cells, which also express TLR3 and can be infected with HSV-1 12,14,17 , may also contribute to HSE.”
Toll-like receptors in the pathogenesis of neuroinflammation
Kumar, V. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.03.012 · Cited by 331 · see citing works
Features of Microglia and Neuroinflammation Relevant to Environmental Exposure and Neurotoxicity
Kraft, A. D., & Harry, G. J. (2011) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph8072980 · Cited by 330 · see citing works
“IL-1β is a major regulator of the expression of several MMPs, it can induce the production of NO, and it can block glutamate uptake.”
BackgroundInfluentialSensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3
Vercammen, E., Staal, J., & Beyaert, R. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00022-07 · Cited by 322 · see citing works
“All these different neuronal cell types have been shown to express TLR3 and initiate signaling upon being triggered with dsRNA or viruses, such as rabies virus and herpes simplex virus type 1 (23, 48, 49, 60, 81).”
BackgroundZhang, S., Boisson‐Dupuis, S., Chapgier, A. L. A., Yang, K., Bustamante, J. C., Puel, A., Pïcard, C., Abel, L., Jouanguy, E., & Casanova, J. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00698.x · Cited by 320 · see citing works
Guo, Y., Audry, M., Ciancanelli, M. J., Alsina, L., Azevedo, J., Casadio, M., Anguiano, E., Sancho‐Shimizu, V., Lorenzo, L., Pauwels, E., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101568 · Cited by 310 · see citing works
“The abundant and almost selective expression of functional TLR3 in the CNS, in both nonhematopoietic (neurons, oligodendrocytes, and astrocytes) and hematopoietic (microglial cells) CNS-resident cells (Bsibsi et al., 2002, 2006; Olson and Miller, 2004; Jack et al., 2005; Préhaud et al., 2005; Peltier et al., 2010), th…”
BackgroundTOLL-LIKE RECEPTORS IN ISCHEMIA-REPERFUSION INJURY
Arumugam, T. V., Okun, E., Tang, S., Thundyil, J., Taylor, S. M., & Woodruff, T. M. (2009) · Shock · doi:10.1097/shk.0b013e318193e333 · Cited by 299 · see citing works
“mRNAs for TLRs 1 to 7, 9, and 10 are detectable in human primary astrocytes cultures shown to be microglia-free using astrocyte-specific GFAP staining (109).”
BackgroundKigerl, K. A., Lai, W., Rivest, S., Hart, R. P., Satoskar, A. R., & Popovich, P. G. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04524.x · Cited by 298 · see citing works
“Conversely, others have failed to identify TLR4 mRNA or protein in astrocytes (Lehnardt et al. 2002; Jack et al. 2005; Mishra et al. 2006).”
BackgroundToll‐like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators
Bsibsi, M., Persoon-Deen, C., Verwer, R. W. H., Meeuwsen, S., Ravid, R., & van Noort, J. M. (2006) · Glia · doi:10.1002/glia.20328 · Cited by 296 · see citing works
“In human astrocytes, however, the TLR expression profile is more restricted both in adult (Bsibsi et al., 2002) and in fetal astrocytes (Farina et al., 2005; Jack et al., 2005).”
BackgroundThe influence of microglia on the pathogenesis of Parkinson's disease
Long-Smith, C. M., Sullivan, A. M., & Nolan, Y. M. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.08.001 · Cited by 296 · see citing works
Bachstetter, A. D., Xing, B., de Almeida, L., Dimayuga, E. R., Watterson, D. M., & Van Eldik, L. J. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-79 · Cited by 282 · see citing works
“Second, microglia have been shown to express these receptors [34].”
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Zhao, W., Beers, D. R., Henkel, J. S., Zhang, W., Urushitani, M., Julien, J., & Appel, S. H. (2010) · Glia · doi:10.1002/glia.20919 · Cited by 288 · see citing works
“Other lines of evidence indeed suggest that CD14/TLRs may contribute to the inflammatory responses initiated by microglia (Jack et al., 2005; Olson and Miller, 2004).”
BackgroundMiyoshi, K., Obata, K., Kondo, T., Okamura, H., & Noguchi, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3512-08.2008 · Cited by 291 · see citing works
“Microglia, the resident myeloid cells that constitute the innate immune system in the CNS, express TLRs (Olson and Miller, 2004; Jack et al., 2005).”
BackgroundGlial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse
Lacagnina, M. J., Rivera, P. D., & Bilbo, S. D. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.121 · Cited by 271 · see citing works
“TLR4, for example, has been observed on microglia, neurons, astrocytes, neural progenitor cells, and endothelial cells (AlfonsoLoeches et al, 2010; Grace et al, 2014b; Jack et al, 2005; June et al, 2015; Liu et al, 2011; Rolls et al, 2007).”
BackgroundThe role of antigen presenting cells in multiple sclerosis
Chastain, E. M. L., Duncan, D. S., Rodgers, J. M., & Miller, S. D. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.008 · Cited by 264 · see citing works
“Human and murine astrocytes also recruit monocytes and T cells by producing significant amounts of CCL2, CCL5, and CXCL10 in response to TMEV infection and polyI:C stimulation [113,115,126].”
Smith, A. M., & Dragunow, M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2013.12.001 · Cited by 256 · see citing works
Wosik, K., Cayrol, R., Dodelet-Devillers, A., Berthelet, F., Bernard, M., Moumdjian, R. A., Bouthillier, A., Reudelhuber, T. L., & Prat, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2088-07.2007 · Cited by 259 · see citing works
“Astrocyte isolation has been described previously (D’Souza et al., 1995; Wosik et al., 2001; Jack et al., 2005).”
MethodToll-like receptor signaling in endogenous neuroprotection and stroke
Marsh, B. J., Williams-Karnesky, R. L., & Stenzel‐Poore, M. P. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.07.067 · Cited by 256 · see citing works
“Microglia initiate robust cytokine and chemokine responses to stimulation of TLR2 (TNFα, IL-6, IL-10), TLR3 (TNFα, IL-6, IL-10, IL-12, CXCL-10, IFNβ), and TLR4 (TNFα, IL-6, IL-10, CXCL-10, IFNβ), yet astrocytes initiate only minor IL-6 responses to all but TLR3 stimulation (Jack et al., 2005).”
BackgroundInfluentialFTY720 modulates human oligodendrocyte progenitor process extension and survival
Miron, V. E., Jung, C., Kim, H. J., Kennedy, T. E., Soliven, B. C., & Antel, J. P. (2007) · Annals of Neurology · doi:10.1002/ana.21227 · Cited by 255 · see citing works
“Actin transcript levels were used as endogenous controls for the amount of RNA transcribed, and primers/ probes were designed using the PRIMER express software.(32) All S1P receptor levels were normalized to the actin levels in the corresponding sample.”
MethodMolecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia
Obrenovitch, T. P. (2008) · Physiological Reviews · doi:10.1152/physrev.00039.2006 · Cited by 250 · see citing works
Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation
Wheeler, M. A., Jaronen, M., Covacu, R., Zandee, S., Scalisi, G., Rothhammer, V., Tjon, E. C., Chao, C., Kenison, J. E., Blain, M., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.012 · Cited by 250 · see citing works
Toll-like receptors in chronic pain
Nicotra, L. L., Loram, L. C., Watkins, L. R., & Hutchinson, M. R. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.09.038 · Cited by 251 · see citing works
“…et al., 2007; Bsibsi, et al., 2006; Butchi et al., 2010; Carpentier et al., 2005; Diogenes et al., 2011; El-Hage et al., 2011; Hou and Wang, 2001; Jack et al., 2005; Kakimura et al., 2002; Krasowska-Zoladek et al., 2007; Li et al., 2004; Mayer et al., 2011; Ochoa-Cortes, et al., 2010; Qi, et…”
Sánchez-Guajardo, V., Barnum, C. J., Tansey, M. G., & Romero‐Ramos, M. (2013) · ASN NEURO · doi:10.1042/an20120066 · Cited by 237 · see citing works
“If not nitrated, no cell death Couch et al., 2011 WT 3 μg Direct intra-SN injection Mice ABH Biozzi ↑mRNA Il-1β, TGFβ and COX2 after 24h If peripheral LPS: unclear results ↑Iba-1 + cells and ICAM + cells after 24h Jin et al., 2007 Endogenous murine MPTP-intoxication-induced murine α-syn aggregation Prostaglandin E2 re…”
BackgroundInfluentialToll-Like Receptor 3 Is a Potent Negative Regulator of Axonal Growth in Mammals
Cameron, J. S., Alexopoulou, L., Sloane, J. A., DiBernardo, A., Ma, Y., Kosaras, B., Flavell, R. A., Strittmatter, S. M., Volpe, J. J., Sidman, R. L., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4290-06.2007 · Cited by 235 · see citing works
“…(Laflamme et al., 2001; Nguyen et al., 2001; Dalpke et al., 2002; Lehnardt et al., 2002, 2003, 2006; Olson and Miller, 2004; Ebert et al., 2005; Jack et al., 2005; Jung et al., 2005; Kielian et al., 2005; Lotz et al., 2005; Su et al., 2005; Zhang et al., 2005; Andaloussi et al., 2006; Esen and…”
BackgroundOxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives
Ermakov, E. A., Dmitrieva, E. M., Parshukova, D. A., Kazantseva, D. V., Vasilieva, A. R., & Smirnova, L. P. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8881770 · Cited by 252 · see citing works
“Microglia express most TLRs, and their expression levels are altered by microglial activation [252].”
BackgroundAntigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain
Becher, B., Bechmann, I., & Greter, M. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0065-1 · Cited by 229 · see citing works
“, CD80, CD86, CD40, ICAM-1, and VCAM-1) upon exposure to IFNγ [106] and are capable of sensing pathogens through toll-like receptors [107].”
BackgroundThe mechanisms of microgliosis and pain following peripheral nerve injury
Calvo, M., & Bennett, D. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.08.018 · Cited by 224 · see citing works
“Microglia express the TLRs 1 to 9 (Jack et al., 2005; Olson and Miller, 2004).”
BackgroundmiR‐155 as a multiple sclerosis–relevant regulator of myeloid cell polarization
Moore, C. S., Rao, V. T. S., Durafourt, B. A., Bedell, B. J., Ludwin, S. K., Bar‐Or, A., & Antel, J. P. (2013) · Annals of Neurology · doi:10.1002/ana.23967 · Cited by 219 · see citing works
Self-citationLong‐COVID syndrome‐associated brain fog and chemofog: Luteolin to the rescue
Theoharides, T. C., Cholevas, C., Polyzoidis, K. S., & Politis, A. M. (2021) · BioFactors · doi:10.1002/biof.1726 · Cited by 219 · see citing works
Antidepressant therapies inhibit inflammation and microglial M1-polarization
Kalkman, H. O., & Feuerbach, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.001 · Cited by 212 · see citing works
Lund, S., Christensen, K. V., Hedtjärn, M., Mortensen, A. L., Hagberg, H., Falsig, J., Hasseldam, H., Schrattenholz, A. S., Pörzgen, P., & Leist, M. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.07.007 · Cited by 212 · see citing works
“Microglia are equipped with a broad range of pattern-recognition receptors of the toll-like receptor family (TLR family) to detect microbial intruders (Jack et al., 2005).”
BackgroundTang, S.-C., Lathia, J. D., Selvaraj, P. K., Jo, D.-G., Mughal, M. R., Cheng, A., Siler, D. A., Markesbery, W. R., Arumugam, T. V., & Mattson, M. P. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.05.014 · Cited by 232 · see citing works
“Some TLRs are present in the brain, where their expression where they are expressed in glial cells (microglia, astrocytes and oligodentrocytes) (Lehnardt et al., 2003; Olson and Miller., 2004; Jack et al., 2005; Walter et al., 2007) and neurons (Lefon et al.”
BackgroundThe Interleukin-10 Family of Cytokines and Their Role in the CNS
Burmeister, A. R., & Marriott, I. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00458 · Cited by 208 · see citing works
“It is clear that both microglia and astrocytes can be a source of IL-10, and that they are responsive to the immunosuppressive actions of this cytokine (Jack et al., 2005; Bsibsi et al., 2006; Rasley et al., 2006; Park et al., 2007; Gautam et al., 2011; Gutierrez-Murgas et al., 2016).”
BackgroundCarpentier, A. C., Métellus, P., Ursu, R., Zohar, S., Lafitte, F., Barrié, M., Meng, Y., Richard, M., Parizot, C., Laigle–Donadey, F., et al. (2010) · Neuro-Oncology · doi:10.1093/neuonc/nop047 · Cited by 204 · see citing works
Toll-like receptors and their role in persistent pain
Lacagnina, M. J., Watkins, L. R., & Grace, P. M. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.10.006 · Cited by 210 · see citing works
“In addition to DRGs, these endosomal-residing TLRs are thought to be expressed in varying degrees on microglia, astrocytes, oligodendrocytes, Schwann cells, fibroblasts, endothelial cells (Bsibsi et al., 2002; Goethals et al., 2010; Jack et al., 2005; Lehmann et al., 2012; Olson & Miller, 2004).”
Immune Players in the CNS: The Astrocyte
Jensen, C., Massie, A., & Keyser, J. D. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9480-6 · Cited by 203 · see citing works
Domínguez-Punaro, M. D. L. C., Segura, M., Plante, M.-M., Lacouture, S., Rivest, S., & Gottschalk, M. G. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.3.1842 · Cited by 200 · see citing works
“Both types of cells express constitutively low levels of mRNA encoding different TLRs which can be notably increased following the binding of specific ligands (23, 24).”
BackgroundInnate Immunity and Neuroinflammation
Shastri, A., Bonifati, D. M., & Kishore, U. (2013) · Mediators of Inflammation · doi:10.1155/2013/342931 · Cited by 201 · see citing works
“IFN-𝛽 therapy is effective in treating inflammasome-dependent disease in mouse models of MS [159].”
BackgroundOspelt, C., & Gay, S. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.10.010 · Cited by 197 · see citing works
Ifergan, I., Kébir, H., Bernard, M., Wosik, K., Dodelet-Devillers, A., Cayrol, R., Arbour, N., & Prat, A. (2007) · Brain · doi:10.1093/brain/awm295 · Cited by 198 · see citing works
Multiple Sclerosis and T Lymphocytes: An Entangled Story
Legroux, L., & Arbour, N. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9614-0 · Cited by 196 · see citing works
“, IL-6, IL-12, IL-23, TNF) (Jack et al. 2005; Strachan-Whaley et al. 2014); although the cytokine levels produced by activated microglia can be lower than those produced by macrophages (Wlodarczyk et al.”
BackgroundZhu, X., Nishimura, F., Sasaki, K., Fujita, M., Dusak, J. E., Eguchi, J., Fellows-Mayle, W. K., Storkus, W. J., Walker, P. R., Salazar, A. Μ., et al. (2007) · Journal of Translational Medicine · doi:10.1186/1479-5876-5-10 · Cited by 194 · see citing works
“In the CNS and CNS tumors, recent studies have reported that both microglia [13] and astrocytes express TLR3 [3,14].”
BackgroundTurco, F., Sarnelli, G., Cirillo, C., Palumbo, I., Giorgi, F. D., D’Alessandro, A., Cammarota, M., Giuliano, M., & Cuomo, R. (2013) · Gut · doi:10.1136/gutjnl-2012-302090 · Cited by 187 · see citing works
Alvarado, A. G., Thiagarajan, P. S., Mulkearns-Hubert, E. E., Silver, D. J., Hale, J. S., Alban, T. J., Turaga, S. M., Jarrar, A., Reizes, O., Longworth, M. S., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2016.12.001 · Cited by 185 · see citing works
“The brain has a distinct set of immune regulatory mechanisms, and diverse TLR expression in neurons, astrocytes, oligodendrocytes, and microglia contributes to normal brain function and homeostasis (Jack et al., 2005; Okun et al., 2009; van Noort and Bsibsi, 2009).”
Toll-Like Receptor 2 Signaling in Response to Brain Injury: An Innate Bridge to Neuroinflammation
Babcock, A. A., Wirenfeldt, M., Holm, T. H., Nielsen, H. H., Dissing‐Olesen, L., Toft‐Hansen, H., Millward, J. M., Landmann, R. M., Rivest, S., Finsen, B. R., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4937-05.2006 · Cited by 186 · see citing works
“Both astrocytes and microglia have been shown to express TLRs in vitro (Olson and Miller, 2004; Carpentier et al., 2005; Jack et al., 2005).”
BackgroundImmune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids
Bartok, E., & Hartmann, G. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.014 · Cited by 184 · see citing works
Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection
Clark, K., Wiley, C. A., & Bradberry, C. W. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9334-7 · Cited by 186 · see citing works
The Innate Immune Facet of Brain: Human Neurons Express TLR-3 and Sense Viral dsRNA
Lafon, M., Mégret, F., Lafage, M., & Prehaud, C. J. N. (2006) · Journal of Molecular Neuroscience · doi:10.1385/jmn:29:3:185 · Cited by 181 · see citing works
TLR3 immunity to infection in mice and humans
Zhang, S., Casadio, M., Ciancanelli, M. J., de Diego, R. P., Sancho‐Shimizu, V., Abel, L., & Casanova, J. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.11.001 · Cited by 179 · see citing works
Rossi, D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.04.003 · Cited by 178 · see citing works
Glial toll-like receptor signaling in central nervous system infection and autoimmunity
Carpentier, P. A., Duncan, D. S., & Miller, S. D. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.08.011 · Cited by 178 · see citing works
“To date, human astrocytes have been reported to express TLRs1-5 and TLR9, also with particularly high expression of TLR3 (Bsibsi et al., 2006; Bsibsi et al., 2002; Jack et al., 2005).”
BackgroundHaslund‐Vinding, J., McBean, G., Jaquet, V, & Vilhardt, F. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13425 · Cited by 169 · see citing works
Microglia Activation and Anti-inflammatory Regulation in Alzheimer’s Disease
Lue, L., Kuo, Y., Beach, T. G., & Walker, D. G. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8106-8 · Cited by 175 · see citing works
“They react to these conditions by changing motility, shape of processes and cell bodies, phagocytic functions, releases of cytokines, chemokines, reactive oxygen species and prostaglandin metabolites, and expression of innate and adaptive immunefunction molecules [13, 18–20].”
Pais, T. F., Szegő, É. M., Marques, O., Miller‐Fleming, L., Antas, P., Guerreiro, P. S., de Oliveira, R. M., Kasapoğlu, B., & Outeiro, T. F. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.200 · Cited by 176 · see citing works
“We analysed several established activation markers, including IL-10 production, which is induced following TLR ligation in microglia (Jack et al , 2005).”
Toll-like Receptors in Defense and Damage of the Central Nervous System
Aravalli, R. N., Peterson, P. K., & Lokensgard, J. R. (2007) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-007-9071-5 · Cited by 173 · see citing works
“In fact, microglia have been reported to express mRNAs for TLRs 1–9 (Lee and Lee 2002; Olson and Miller 2004; Jack et al. 2005; McKimmie and Fazakerley 2005; Jung et al. 2005), whereas neurons (Prehaud et al.”
BackgroundReinert, L. S., Harder, L., Holm, C. K., Iversen, M. B., Horan, K., Dagnæs‐Hansen, F., Ulhøi, B. P., Holm, T. H., Mogensen, T. H., Owens, T., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60893 · Cited by 171 · see citing works
“Since, TLR3 is reported to be highly expressed by astrocytes (30–33), we focused on this cell type.”
Role of ninjurin‐1 in the migration of myeloid cells to central nervous system inflammatory lesions
Ifergan, I., Kébir, H., Terouz, S., Alvarez, J. I., Lécuyer, M., Gendron, S., Bourbonnière, L., Dunay, I. R., Bouthillier, A., Moumdjian, R. A., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22519 · Cited by 167 · see citing works
Anti-inflammatory Effects of Curcumin in Microglial Cells
Yu, Y., Shen, Q., Lai, Y., Park, S. Y., Ou, X., Lin, D., Jin, M., & Zhang, W. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00386 · Cited by 166 · see citing works
“Microglia express pattern recognition receptors (PRR) that can bind to pattern-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively (Jack et al., 2005).”
BackgroundMicroglia and Astrocyte Function and Communication: What Do We Know in Humans?
Garland, E. F., Hartnell, I. J., & Boche, D. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.824888 · Cited by 165 · see citing works
Human Toll‐like receptor‐dependent induction of interferons in protective immunity to viruses
Zhang, S., Jouanguy, E., Sancho‐Shimizu, V., von Bernuth, H., Yang, K., Abel, L., Pïcard, C., Puel, A., & Casanova, J. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00564.x · Cited by 166 · see citing works
“Many in vitro studies have shown that a functional TLR3 is expressed in these cell types, which produce IFN-a, -b, -l and other cytokines and chemokines in response to poly(I:C) stimulation, presumably via TLR3 (68, 112, 113, 115, 118, 119, 121) .”
BackgroundGlial influences on BBB functions and molecular players in immune cell trafficking
Lécuyer, M., Kébir, H., & Prat, A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.004 · Cited by 163 · see citing works
Ronaldson, P. T., & Davis, T. P. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212802002625 · Cited by 157 · see citing works
Toll‐like receptor expression in the peripheral nerve
Goethals, S., Ydens, E., Timmerman, V., & Janssens, S. (2010) · Glia · doi:10.1002/glia.21041 · Cited by 157 · see citing works
“In the nervous system, especially microglial cells appear to express a broad range of TLRs and as such are endowed with a sentinel function in the brain (Bsibsi et al., 2002; Jack et al., 2005; Olson and Miller, 2004).”
BackgroundMicroglial activation in the pathogenesis of Huntington's disease
Yang, H.-M., Yang, S., Huang, S.-S., Tang, B.-S., & Guo, J.-F. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00193 · Cited by 151 · see citing works
“TLR-2 is the most expressed TLR in microglia, which is responsible for IL-6 and IL-10 secretion.”
BackgroundInfluentialToll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies
Ménager, P., Roux, P., Mégret, F., Bourgeois, J., Sourd, A. L., Danckaert, A., Lafage, M., Prehaud, C. J. N., & Lafon, M. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000315 · Cited by 152 · see citing works
“High levels of TLR3 are found in glial cells [15,16] and neurons in”
BackgroundToll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle
Sukkar, M. B., Xie, S., Khorasani, N. M., Kon, O. M., Stanbridge, R. D. L., Issa, R., & Chung, K. F. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.05.013 · Cited by 151 · see citing works
Crowley, T., Cryan, J. F., Downer, E. J., & O’Leary, O. F. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.02.001 · Cited by 150 · see citing works
“…resident CNS cells continues to be elucidated, with complements of receptors expressed on microglia (TLRs 1-9) (Aravalli et al., 2007; Jack et al., 2005), astrocytes (TLRs 1-5, 9) (Jack et al., 2005; Mishra et al., 2008), and neurons (TLRs 2-5, 8, 9, 11-12) (Ma et al., 2006; Mishra et al., 2008).”
BackgroundDysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02325-6 · Cited by 152 · see citing works
- Authors
- Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., Shapiro, A., & Antel, J. P.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-10-01
- Volume
- 175
- Issue
- 7
- Pages
- 4320-4330
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2165413779
- Cited by
- 734
- References
- 46
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 15 · 2023: 34 · 2022: 44 · 2021: 42 · 2020: 25 · 2019: 26 · 2018: 36 · 2017: 39 · 2016: 38 · 2015: 40 · 2014: 33 · 2013: 59 · 2012: 44
- FWCI
- 20.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Toll-like receptors, microglia, astrocytes, glial activation, TLR3, TLR4, TLR2, MyD88 signaling, neuroinflammation, inflammatory cytokines, CXCL10, IL-10, interferon-beta, innate immunity
- MeSH terms
- Adult, Antigens, Differentiation, Astrocytes, Fetus, Humans, Immunity, Innate, Receptors, Immunologic, Signal Transduction, Interleukin-10, Microglia, Interleukin-12, Adaptor Proteins, Signal Transducing, Myeloid Differentiation Factor 88
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