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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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“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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Toll‐like receptors in neuroinflammation, neurodegeneration, and alcohol‐induced brain damage
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“These receptors are expressed on cells active in innate immunity, but are also found on glial (microglia and astrocytes) and non-glial (spinal and DRG neurons) CNS cells [25-27].”
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“It is also known that microglia can express mRNA for all Toll-like receptors except Toll-like receptor 10 and therefore can recognize pattern-recognition receptors, which can be especially important in the immature neonatal brain.(136)”
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Rodríguez‐Carballeira, M., Solans, R., Larrañaga, J. R., García-Hernández, F. J., Ríos-Fernández, R., Nieto, J., Solanich, X., Martínez‐Valle, F., Fonseca, E., Muñoz, F. J., et al. (2017) · PubMed · Cited by 107
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“In astrocytes TLR3 signaling induces the strongest pro-inflammatory response involving secretion of high levels of IL-12, TNF-a, IL-6, CXCL-10 (IP10), and IL-10.”
Gowing, G., Dequen, F., Soucy, G., & Julien, J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0602-06.2006 · Cited by 105
“Moreover, TLR-2 has been found to ligate a broad array of ligands, both pathogen associated and endogenously derived (Jack et al., 2005).”
BackgroundAstrocytes produce interferon‐alpha and CXCL10, but not IL‐6 or CXCL8, in aicardi‐Goutières syndrome
van Heteren, J., Rozenberg, F., Aronica, E., Troost, D., Lebon, P., & Kuijpers, T. W. (2008) · Glia · doi:10.1002/glia.20639 · Cited by 106
“…play a central role in innate immunity of the CNS. Astrocytes express several toll-like receptors, such as TLR2, TLR3, TLR4, and TLR9, as well as several cytosolic receptors that can recognize pathogens (Bowman et al., 2003; Carpentier et al., 2007; Farina et al., 2005; Jack et al., 2005).”
BackgroundSaikali, P., Antel, J. P., Newcombe, J., Chen, Z., Freedman, M. S., Blain, M., Cayrol, R., Prat, A., Hall, J. A., & Arbour, N. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4402-06.2007 · Cited by 104
“Total RNA was isolated using TRIzol (Invitrogen) and the Qiagen (Mississauga, Ontario, Canada) RNeasy mini kit according to the manufacturer’s instructions and as described previously (Jack et al., 2005).”
BackgroundMethodInfluentialType I interferon response in the central nervous system
Paul, S., Ricour, C., Sommereyns, C., Sorgeloos, F., & Michiels, T. (2007) · Biochimie · doi:10.1016/j.biochi.2007.02.009 · Cited by 105
Systemic Inflammation Perturbs Developmental Retinal Angiogenesis and Neuroretinal Function
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Spinal glial TLR4‐mediated nociception and production of prostaglandin E 2 and TNF
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“The functional expression of these receptor proteins in astrocytes is further supported by the ability of TLR4 ligands to induce both mRNA expression and protein secretion of pro-inflammatory cytokines from astrocytes (Bowman et al., 2003; Jack et al., 2005).”
BackgroundThe innate immunity of the central nervous system in chronic pain: The role of Toll-like receptors
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“A number of studies have demonstrated that NF-κB and MAPKs have important roles in modulating the expression of pro-inflammatory cytokines and iNOS in LPS-stimulated microglia [19,20].”
BackgroundJackson, A. C., Rossiter, J. P., & Lafon, M. (2006) · Journal of NeuroVirology · doi:10.1080/13550280600848399 · Cited by 102
“This is consistent with the previous in vitro finding that fetal astrocytes express TLR-3 (Farina et al, 2005; Jack et al, 2005) and the observation of enhanced glial expression of TLR-3 in multiple sclerosis white matter lesions (Bsibsi et al, 2002).”
BackgroundResultContribution of Astrocyte-Derived IL-15 to CD8 T Cell Effector Functions in Multiple Sclerosis
Saikali, P., Antel, J. P., Pittet, C. L., Newcombe, J., & Arbour, N. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002188 · Cited by 101
“, IL-6) (41) that can activate T cells.”
BackgroundMethodInfluentialKim, K. S., Kim, J.-S., Park, J. Y., Suh, Y. H., Jou, I., Joe, E.-H., & Park, S. M. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt332 · Cited by 102
“While immature monocyte-derived dendritic cells andbloodmyeloiddendritic cells expressTLR3exclusively intracellularly,fibroblasts, epithelial cells andastrocytes express TLR3 both intracellularly and on the cell surface (42,43).”
BackgroundMemory-Like Inflammatory Responses of Microglia to Rising Doses of LPS: Key Role of PI3Kγ
Lajqi, T., Lang, G.-P., Haas, F., Williams, D. L., Hudalla, H., Bauer, M. W., Groth, M., Wetzker, R., & Bauer, R. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02492 · Cited by 99
“Indeed, the time frame of a single PAMPinduced neuroinflammatory response is composed of an initial massive pro-inflammatory response peaking within few hours followed by a resolution phase induced by delayed secondary production of mediators that are immunosuppressive and/or neuroprotective 24–48 h later (51, 54).”
BackgroundVerzosa, A. L., McGeever, L. A., Bhark, S., Delgado, T., Salazar, N., & Sanchez, E. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.644664 · Cited by 107
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“The synthetic TLR3 ligand poly(I:C) (PIC) is a potent activator of rat, murine, and human astrocytes (34, 59, 65, 72).”
BackgroundMethodInfluentialRole of toll-like receptors in multiple sclerosis.
Miranda‐Hernandez, S., & Baxter, A. G. (2013) · Europe PMC (PubMed Central) · Cited by 96
Blanco, A. M. A. (2006) · Frontiers in bioscience · doi:10.2741/2259 · Cited by 97
“However, a robust expression of TLR3 has been demonstrated in adult and fetal astrocytes (55, 56), along with low levels of expression for TLR 1, 4, 2, 5 and 9 on human fetal astrocytes (11).”
BackgroundInfluentialEffects of Curcumin on Microglial Cells
Ghasemi, F., Bagheri, H., Barreto, G. E., Read, M. I., & Sahebkar, A. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00030-0 · Cited by 97
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Impaired monocyte activation in schizophrenia
Müller, N., Wagner, J. K., Krause, D., Weidinger, E., Wildenauer, A., Obermeier, M., Dehning, S., Gruber, R., & Schwarz, M. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2011.12.049 · Cited by 97
“Toll-like receptors (TLRs) are expressed on humanmonocytes andmicroglia (Jack et al., 2005), involved in the regulation of the CNS immune response and suggested to be the link between the immune system and the CNS (Downes and”
Zhu, X., Fallert-Junecko, B., Fujita, M., Ueda, R., Kohanbash, G., Kastenhuber, E. R., McDonald, H. A., Liu, Y., Kaliński, P., Reinhart, T. A., et al. (2010) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-010-0876-3 · Cited by 95
“As TLR3 stimulation efficiently induces production of pro-inflammatory cytokines and chemokines, including CXCL10/IP-10 from astrocytes and microglia [19–21], we hypothesized that the combination treatment of GAA-vaccine and poly-ICLC would enhance CXCL10 expression in the glioma microenvironment as a key mediator for…”
Cyclical and Dose-Dependent Responses of Adult Human Mature Oligodendrocytes to Fingolimod
Miron, V. E., Hall, J. A., Kennedy, T. E., Soliven, B. C., & Antel, J. P. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080478 · Cited by 96
“-Actin transcript levels were used as endogenous controls for the amount of RNA transcribed, and primers/probes were designed using the PRIMER express software (Applied Biosystems).(41) All S1P receptor levels were normalized to the -actin levels in the corresponding sample.”
MethodMarinelli, C., Liddo, R. D., Facci, L., Bertalot, T., Conconi, M. T., Zusso, M., Skaper, S. D., & Giusti, P. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0458-6 · Cited by 92
“[39, 63], inhibition of translational machinery [64], negative regulation by pro-inflammatory cytokines [65] and endocytic pathways [66].”
BackgroundResultInfluentialPathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases
Ghasemi, M., & Fatemi, A. S. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.06.002 · Cited by 103
El‐Hage, N., Podhaizer, E. M., Sturgill, J., & Hauser, K. F. (2011) · Immunological Investigations · doi:10.3109/08820139.2011.561904 · Cited by 96
“TLR3, which recognizes dsRNA (Bsibsi et al., 2006; Carpentier et al., 2005; Jack et al., 2005; Lafon et al., 2006; McKimmie and Fazakerley, 2005; Rivieccio et al., 2006), suggesting that astrocytes may be particularly important for anti-viral responses in the CNS.”
BackgroundZalpoor, H., Akbari, A., Samei, A., Forghaniesfidvajani, R., Kamali, M., Afzalnia, A., Manshouri, S., Heidari, F., Pornour, M., Khoshmirsafa, M., et al. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-022-00311-1 · Cited by 92
“Astrocytes are endogenous cells of CNS that play critical roles in immune responses [25].”
BackgroundInterplay Between Exosomes, microRNAs and Toll-Like Receptors in Brain Disorders
Paschon, V., Takada, S. H., Ikebara, J. M., de Sousa, É., Raeisossadati, R., Ulrich, H., & Kihara, A. H. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9142-1 · Cited by 95
“Human microglia expresses TLR1–4 proteins [86, 87, 90], and murine microglia expresses TLR2, 4”
BackgroundRosenberger, K., Derkow, K., Dembny, P., Krüger, C., Schott, E., & Lehnardt, S. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0166-7 · Cited by 84
“All cells of the CNS express TLRs, while each cell type displays its own subset of differentially expressed TLRs and related signaling adaptor proteins [5-10].”
BackgroundKinetics of inflammatory response of astrocytes induced by TLR 3 and TLR4 ligation
Krasowska‐Zoladek, A., Banaszewska, M., Kraszpulski, M., & Konat, G. W. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21088 · Cited by 91
“, 2005) and human (Jack et al., 2005) astrocytes.”
BackgroundInfluentialSchilling, S., Chausse, B., Dikmen, H. O., Almouhanna, F., Hollnagel, J., Lewen, A., & Kann, O. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.05.013 · Cited by 91
Anti-inflammatory treatment in schizophrenia
Müller, N., Myint, A.-M., Krause, D., Weidinger, E., & Schwarz, M. J. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.11.008 · Cited by 89
Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury
Bohaček, I., Cordeau, P., Lalancette–Hébert, M., Gorup, D., Weng, Y.-C., Gajović, S., & Križ, J. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-191 · Cited by 89
“After brain injury and/ or pathogen exposition, TLR2 is mainly expressed in the population of microglial cells [11,20,38,39].”
BackgroundMattioli, T.-A. M., Leduc‐Pessah, H., Skelhorne‐Gross, G., Nicol, C. J. B., Milne, B., Trang, T., & Cahill, C. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097361 · Cited by 89
“Hutchinson and colleagues pioneered studies demonstrating that morphine and other opioid agonists have off-target effects at toll-like receptor 4 (TLR4) receptors [17,18], which are widely expressed in spinal microglia, macrophages [19,20], and astrocytes [21,22–24].”
BackgroundStenzel, W., Soltek, S., Sánchez-Ruiz, M., Akira, S., Miletic, H., Schlüter, D., & Deckert, M. (2008) · American Journal of Pathology · doi:10.2353/ajpath.2008.070567 · Cited by 96
A Clear and Present Danger: Endogenous Ligands of Toll-like Receptors
Sloane, J. A., Blitz, D., Margolin, Z. R., & Vartanian, T. K. (2009) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8094-x · Cited by 86
“Thus, it is not surprising that most groups indicate that TLR stimulation induces preferential induction of TLR3 mRNA in astrocytes (Bsibsi et al. 2006; Jack et al. 2005).”
BackgroundMethodInfluentialRole of microglia-neuron interactions in diabetic encephalopathy
Liu, Y., Li, M., Zhang, Z., Ye, Y., & Zhou, J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.12.005 · Cited by 88
Microglia–Astrocyte Interaction in Neural Development and Neural Pathogenesis
Sun, M., You, H., Hu, X., Luo, Y., Zhang, Z., Song, Y., An, J., & Lü, H. (2023) · Cells · doi:10.3390/cells12151942 · Cited by 90
“Glial cell interaction in neurodegenerative diseases is triggered by the binding of DAMPs either to the Toll-like receptors (TLRs) on the cell membranes of microglia and astrocytes or to the intracellular receptors through endocytosis, resulting in downstream signaling activation [83].”
BackgroundInfluentialToll-Like Receptors: Insights into Their Possible Role in the Pathogenesis of Lyme Neuroborreliosis
Bernardino, A., Myers, T. A., Alvarez, X. A., Hasegawa, A., & Philipp, M. T. (2008) · Infection and Immunity · doi:10.1128/iai.00394-08 · Cited by 87
Müller, N., Myint, A.-M., & Schwarz, M. (2012) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-398314-5.00003-9 · Cited by 86
Oleoylethanolamide, Neuroinflammation, and Alcohol Abuse
Orío, L., Alén, F., Pavón, F. J., Serrano, A., & García‐Bueno, B. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00490 · Cited by 91
“As mentioned before, TLRs are activated by PAMPs and they are highly expressed in glial cells (Jack et al., 2005).”
BackgroundToll-like receptor-induced cytokines as immunotherapeutic targets in cancers and autoimmune diseases
Patra, M. C., Shah, M., & Choi, S. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.05.002 · Cited by 84
Brain-Region-Specific Astroglial Responses In Vitro After LPS Exposure
Kipp, M., Norkutė, A., Johann, S., Lorenz, L., Braun, A., Hieble, A., Gingele, S., Pott, F., Richter, J., & Beyer, C. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-008-9057-7 · Cited by 86
“The TLR family is a major class of patternrecognition receptors that has emerged as a central player in the initiation and tailoring of both innate and subsequent adaptive immune responses (Jack et al. 2005).”
BackgroundMicroglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation
Kees, T., Lohr, J., Noack, J., Mora-Rodríguez, R. A., Gdynia, G., Toedt, G., Ernst, A., Radlwimmer, B., Falk, C. S., Herold‐Mende, C. C., et al. (2011) · Neuro-Oncology · doi:10.1093/neuonc/nor182 · Cited by 86
“Human microglia isolated from healthy brain are highly reactive to poly (I:C) and respond by secreting cytokines like TNF-a and IL-6.”
Zhou, S., Halle, A., Kurt‐Jones, E. A., Cerny, A., Porpiglia, E., Rogers, M., Golenbock, D. T., & Finberg, R. W. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.11.018 · Cited by 86
“These data are consistent with the concept that LCMVand other PAMPs utilize the same “activation-induced feedback loop” to regulate the expression of TLR2 (Esen and Kielian, 2006; Jack et al., 2005).”
ResultCrocker, S., Frausto, R., Whitton, J., & Milner, R. (2008) · Glia · doi:10.1002/glia.20689 · Cited by 88
“This lack of response to LPS is consistent with the demonstration that astrocytes express only low levels of the LPS receptor TLR4 (Jack et al., 2005; Lehnardt et al., 2003; Lehnart et al., 2002).”
Réus, G. Z., Manosso, L. M., Quevedo, J., & Carvalho, A. F. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105425 · Cited by 94
Microglia and Astrocyte Activation by Toll‐Like Receptor Ligands: Modulation by PPAR‐γ Agonists
Gurley, C. M., Nichols, J. R., Liu, S., Phulwani, N. K., Esen, N., & Kielian, T. (2008) · PPAR Research · doi:10.1155/2008/453120 · Cited by 88
Guo, Y.-J., Luo, T., Wu, F., Mei, Y.-W., Peng, J., Liu, H., Li, H., Zhang, S., Dong, J.-H., Fang, Y., et al. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.01.036 · Cited by 83
Knerlich‐Lukoschus, F., Juraschek, M., Blömer, U., Lucius, R., Mehdorn, H. M., & Held‐Feindt, J. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2007.0431 · Cited by 83
“It is described to be located in microglial and to a lesser extend astroglial cells (Jack et al., 2005).”
Tajalli-Nezhad, S., Karimian, M., Beyer, C., Atlasi, M. A., & Tameh, A. A. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2953-2 · Cited by 83
Yu, S., Wang, X., He, X., Wang, Y., Gao, S., Ren, L., & Shi, Y. (2016) · Cell Stress and Chaperones · doi:10.1007/s12192-016-0695-3 · Cited by 82
IFN‐β regulates CD73 and adenosine expression at the blood–brain barrier
Niemelä, J., Ifergan, I., Yegutkin, G. G., Jalkanen, S., Prat, A., & Airas, L. M. (2008) · European Journal of Immunology · doi:10.1002/eji.200838437 · Cited by 83
Vivithanaporn, P., Maingat, F. G., Lin, L., Na, H., Richardson, C. D., Agrawal, B., Cohen, É. A., Jhamandas, J. H., & Power, C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012856 · Cited by 81
“Microglia/macrophages are known to express both receptors [71,72] while astrocytes express gC1qR but not TLR2 [72,73] and there was a 30% increase in the gC1qR transcript level in HIVinfected brains (Figure S2B).”
BackgroundColleselli, K., Stierschneider, A., & Wiesner, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512464 · Cited by 93
Viral CNS infections: role of glial pattern recognition receptors in neuroinflammation
Furr, S. R., & Marriott, I. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00201 · Cited by 77
“…constitutively express low levels of TLR3 (Jack et al., 2005; Bsibsi et al., 2006), TLR7 (Jack et al., 2005), and TLR9 (Bowman et al., 2003; Jack et al., 2005), but such expression shows marked upregulation following viral infection and/or stimulation with viral components (Bowman et al.,…”
BackgroundResultInfluentialFrazão, J. B., Errante, P. R., & Condino‐Neto, A. (2013) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-013-0243-0 · Cited by 82
Sárvári, M., Hrabovszky, E., Kalló, I., Solymosi, N., Tóth, K., Likó, I., Széles, J., Mahó, S., Molnar, B. A., & Liposits, Z. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-82 · Cited by 84
“We found several genes, such as Mpeg1 [48], Cx3cr1 [49], Cd11b [50], Tlr4 [51] and Tlr9 [52] which are expressed predominantly in microglia, and were suppressed by E2.”
BackgroundInfluentialThe role of regulatory T cells in neurodegenerative diseases
HeFeng, F. Q., & Balling, R. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1187 · Cited by 80
Sárvári, M., Hrabovszky, E., Kalló, I., Solymosi, N., Likó, I., Berchtold, N. C., Cotman, C. W., & Liposits, Z. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-264 · Cited by 81
“Although the microglial response is signal-specific, activated microglia unfold strong macrophage characteristics and express elevated levels of phagocytic [29], scavenger [30] and toll-like [31] receptors (Tlrs), MHC antigens [32].”
BackgroundThe roles of microglia and astrocytes in neuroinflammation of Alzheimer’s disease
Han, J., Zhang, Z., Zhang, P., Yu, Q., Cheng, Q., Lu, Z., & Zong, S. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1575453 · Cited by 97
“Microglia express TLRs 1 to 9, whereas astrocytes express TLR3 in high level but TLRs 1, 4, 5, and 9 in low levels (Jack et al., 2005).”
Metadata
- 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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