CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer
Open accessAbstract
In atherosclerosis and Alzheimer's disease, deposition of the altered self components oxidized low-density lipoprotein (LDL) and amyloid-beta triggers a protracted sterile inflammatory response. Although chronic stimulation of the innate immune system is believed to underlie the pathology of these diseases, the molecular mechanisms of activation remain unclear. Here we show that oxidized LDL and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6. Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, a common receptor for these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation and suggest a new model of TLR heterodimerization triggered by coreceptor signaling events.
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Amyloid-beta-mediated release of proinflammatory factors and neurotoxicity partially involves signaling through the CD36/TLR4/TLR6 complex.
“Stewart and colleagues demonstrated that Aβ-mediated release of proinflammatory factors and neurotoxicity partially involved signaling through the CD36/ TLR4/TRL6 complex (108).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [108]
The CD36/TLR4/TLR6 co-receptor complex upregulates production of chemokines and cytokines such as pro-IL-1β through activation of NF-κB.
“CD36 mediates heterodimer formation of TLR4 and TLR6 (REF. 104), and this co-receptor complex upregulates the production of chemokines and cytokines such as pro-IL-1β through the activation of NF-κb.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [105]
Soluble Aβ oligomers and Aβ fibrils can react to various receptors expressed by microglia, including CD14, CD36, CD47, α6β1 integrin, class A scavenger receptor, RAGE and TLRs.
“The Soluble Aβ oligomers and Aβ fibrils can react to various receptors expressed by microglia, including CD14, CD36, CD47, α6β1 integrin, class A scavenger receptor, receptor for advanced glycosylation end products (RAGE) and TLRs (Stewart et al., 2010).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Stewart et al., 2010
The binding of Aβ to CD36 promotes TLR4 and/or TLR6 phosphorylation and activation, resulting in production of inflammatory cytokines and chemokines.
“The binding of Aβ to CD36 (cell surface microglial co-receptor) promotes the TLR4 and/or TLR6 phosphorylation and activation, resulting in the production of inflammatory cytokines and chemokines (Stewart et al., 2010).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Stewart et al., 2010
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Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725 · see citing works
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
Recognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862 · see citing works
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441 · see citing works
Self-citationOzinsky, A., Underhill, D. M., Fontenot, J. D., Hajjar, A. M., Smith, K. D., Wilson, C. B., Schroeder, L. A., & Aderem, A. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250476497 · Cited by 2,086 · see citing works
Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2
Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S., & Underhill, D. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021787 · Cited by 1,644 · see citing works
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · see citing works
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
Kagan, J. C., Su, T., Horng, T., Chow, A. Y., Akira, S., & Medzhitov, R. M. (2008) · Nature Immunology · doi:10.1038/ni1569 · Cited by 1,256 · see citing works
Kunjathoor, V., Febbraio, M., Podrez, E., Moore, K., Andersson, L., Koehn, S. L., Rhee, J. S., Silverstein, R., Hoff, H., & Freeman, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209649200 · Cited by 1,064 · see citing works
Self-citationImmortalization of murine microglial cells by a v-raf / v-myc carrying retrovirus
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90073-v · Cited by 1,053 · see citing works
Toll-like Receptor 4 Polymorphisms and Atherogenesis
Kiechl, S. J., Lorenz, E., Reindl, M., Wiedermann, C. J., Oberhollenzer, F., Bonora, E., Willeit, J., & Schwartz, D. A. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012673 · Cited by 1,024 · see citing works
Michelsen, K. S., Wong, M. H., Shah, P. K., Zhang, W., Yano, J., Doherty, T. M., Akira, S., Rajavashisth, T. B., & Arditi, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403249101 · Cited by 1,019 · see citing works
CD36 is a sensor of diacylglycerides
Hoebe, K., Georgel, P., Rutschmann, S., Du, X., Mudd, S., Crozat, K., Sovath, S., Shamel, L., Hartung, T., Zähringer, U., et al. (2005) · Nature · doi:10.1038/nature03253 · Cited by 873 · see citing works
Inflammatory processes in Alzheimer's disease
Heneka, M. T., & O'Banion, M. K. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.017 · Cited by 782 · see citing works
Lack of Interleukin-1β Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice
Kirii, H., Niwa, T., Yamada, Y., Wada, H., Saito, K., Iwakura, Y., Asano, M., Moriwaki, H., & Seishima, M. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000064374.15232.c3 · Cited by 748 · see citing works
The inflammasome: a danger sensing complex triggering innate immunity
Pétrilli, V., Dostert, C., Muruve, D. A., & Tschopp, J. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.09.002 · Cited by 700 · see citing works
Björkbacka, H., Kunjathoor, V. V., Moore, K. J., Koehn, S., Ordija, C. M., Lee, M. A., Means, T., Halmen, K., Luster, A. D., Golenbock, D. T., et al. (2004) · Nature Medicine · doi:10.1038/nm1008 · Cited by 634 · see citing works
Self-citationScavenger Receptors in Atherosclerosis: Beyond Lipid Uptake
Moore, K. J., & Freeman, M. W. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000229218.97976.43 · Cited by 562 · see citing works
Self-citationIntracellular signalling controlling integrin activation in lymphocytes
Kinashi, T. (2005) · Nature reviews. Immunology · doi:10.1038/nri1646 · Cited by 555 · see citing works
Modulation of atherosclerosis in mice by Toll-like receptor 2
Mullick, A. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25482 · Cited by 549 · see citing works
Role of the Toll-Like Receptor 4 in Neuroinflammation in Alzheimer’s Disease
Walter, S., Letiembre, M., Liu, Y., Heine, H., Penke, B., Hao, W., Bode, B., Manietta, N., Walter, J., Schulz-Schüffer, W., et al. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000110455 · Cited by 543 · see citing works
A CD36-dependent signaling cascade is necessary for macrophage foam cell formation
Rahaman, S. O., Lennon, D. J., Febbraio, M., Podrez, E. A., Hazen, S. L., & Silverstein, R. L. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.06.007 · Cited by 506 · see citing works
CD36 Mediates the Innate Host Response to β-Amyloid
El Khoury, J. B., Moore, K. J., Means, T. K., Leung, J., Terada, K., Toft, M., Freeman, M. W., & Luster, A. D. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021546 · Cited by 483 · see citing works
Self-citationStuart, L. M., Deng, J., Silver, J. M., Takahashi, K., Tseng, A. A., Hennessy, E. J., Ezekowitz, R. A. B., & Moore, K. J. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200501113 · Cited by 417 · see citing works
Self-citationCoraci, I. S., Husemann, J., Berman, J. W., Hulette, C., Dufour, J. H., Campanella, G. K., Luster, A. D., Silverstein, S. C., & El Khoury, J. B. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64354-4 · Cited by 398 · see citing works
Self-citationMoore, K. J., Kunjathoor, V. V., Koehn, S. L., Manning, J. J., Tseng, A. A., Silver, J. M., McKee, M. L., & Freeman, M. W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24061 · Cited by 371 · see citing works
Self-citationQi, Y., Wang, J. K. T., McMillian, M., & Chikaraishi, D. M. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-04-01217.1997 · Cited by 330 · see citing works
A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid
Moore, K. J., El Khoury, J., Medeiros, L. A., Terada, K., Geula, C., Luster, A. D., & Freeman, M. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208788200 · Cited by 327 · see citing works
Self-citationJin, J.-J., Kim, H.-D., Maxwell, J. A., Li, L., & Fukuchi, K. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-23 · Cited by 272 · see citing works
Association of the Toll-Like Receptor 4 Gene Asp299Gly Polymorphism With Acute Coronary Events
Ameziane, N., Beillat, T., Verpillat, P., Chollet‐Martin, S., Aumont, M.-C., Seknadji, P., Lamotte, M., Lebret, D., Ollivier, V., & de Prost, D. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000101191.92392.1d · Cited by 241 · see citing works
Visintin, A., Mazzoni, A., Spitzer, J. A., & Segal, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211445098 · Cited by 230 · see citing works
Divergent Response to LPS and Bacteria in CD14-Deficient Murine Macrophages
Moore, K. J., Andersson, L. P., Ingalls, R. R., Monks, B. G., Li, R., Arnaout, M. A., Golenbock, D. T., & Freeman, M. W. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.8.4272 · Cited by 226 · see citing works
Self-citationMullick, A. E., Soldau, K., Kiosses, W. B., Bell, T. A., Tobias, P. S., & Curtiss, L. K. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071096 · Cited by 223 · see citing works
Janabi, M., Yamashita, S., Hirano, K., Sakai, N., Hiraoka, H., Matsumoto, K., Zhang, Z., Nozaki, S., & Matsuzawa, Y. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.8.1953 · Cited by 205 · see citing works
Role of TLR4 Tyrosine Phosphorylation in Signal Transduction and Endotoxin Tolerance
Medvedev, A. E., Piao, W., Shoenfelt, J. L., Rhee, S. H., Chen, H., Basu, S., Wahl, L. M., Fenton, M. J., & Vogel, S. N. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m606781200 · Cited by 186 · see citing works
Chi, H.-H., Messas, E., Levine, R. A., Graves, D. T., & Amar, S. (2004) · Circulation · doi:10.1161/01.cir.0000142085.39015.31 · Cited by 173 · see citing works
Minoretti, P., Gazzaruso, C., Vito, C. D., Emanuele, E., Bianchi, M., Coen, E., Reino, M., & Geroldi, D. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.08.047 · Cited by 164 · see citing works
Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome
Ip, W., Takahashi, K., Moore, K. J., Stuart, L. M., & Ezekowitz, R. A. B. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071164 · Cited by 163 · see citing works
Self-citationReactive Oxygen and Nitrogen Species in Alzheimers Disease
Aslan, M., & Özben, T. (2004) · Current Alzheimer Research · doi:10.2174/1567205043332162 · Cited by 97 · see citing works
A Toll-like receptor 2–integrin β3 complex senses bacterial lipopeptides via vitronectin
Gerold, G., Ajaj, K. A., Bienert, M., Laws, H., Zychlinsky, A., & de Diego, J. L. (2008) · Nature Immunology · doi:10.1038/ni.1618 · Cited by 85 · see citing works
Roberson, S. M., & Walker, W. S. (1988) · Cellular Immunology · doi:10.1016/0008-8749(88)90236-5 · Cited by 81 · see citing works
Sun, B., Boyanovsky, B. B., Connelly, M. A., Shridas, P., van der Westhuyzen, D. R., & Webb, N. R. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700163-jlr200 · Cited by 80 · see citing works
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The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304 · see citing works
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Self-citationNLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026 · see citing works
Self-citationMechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580 · 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
Toll-Like Receptor Signaling Pathways
Kawasaki, T., & Kawai, T. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00461 · Cited by 3,250 · see citing works
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Macrophages in the Pathogenesis of Atherosclerosis
Moore, K. J., & Tabas, I. (2011) · Cell · doi:10.1016/j.cell.2011.04.005 · Cited by 2,669 · see citing works
Self-citationMacrophages in atherosclerosis: a dynamic balance
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559 · see citing works
Self-citationAtherosclerosis: current pathogenesis and therapeutic options
Weber, C., & Noels, H. (2011) · Nature Medicine · doi:10.1038/nm.2538 · Cited by 2,203 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Neuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-98 · Cited by 1,748 · see citing works
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
Cholesterol, inflammation and innate immunity.
Tall, A. R., & Yvan-Charvet, L. (2015) · Nature Reviews Immunology · doi:10.1038/nri3793 · Cited by 1,479 · see citing works
Innate Immune Pattern Recognition: A Cell Biological Perspective
Brubaker, S. W., Bonham, K. S., Zanoni, I., & Kagan, J. C. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112240 · Cited by 1,475 · see citing works
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · see citing works
Helical Assembly in the MyD88-IRAK4-IRAK2 Complex in TLR/IL-1R Signalling
Lin, S.-C., Lo, Y.-C., & Wu, H. (2010) · Nature · doi:10.1038/nature09121 · Cited by 1,111 · see citing works
NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis
Grebe, A., Hoss, F., & Latz, E. (2018) · Circulation Research · doi:10.1161/circresaha.118.311362 · Cited by 926 · see citing works
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902 · see citing works
Self-citationSheedy, F. J., Grebe, A., Rayner, K. J., Kalantari, P., Ramkhelawon, B., Carpenter, S. B., Becker, C. E., Ediriweera, H. N., Mullick, A. E., Golenbock, D. T., et al. (2013) · Nature Immunology · doi:10.1038/ni.2639 · Cited by 935 · see citing works
Self-citationInflammation and Lipid Signaling in the Etiology of Insulin Resistance
Glass, C. K., & Olefsky, J. M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.001 · Cited by 942 · see citing works
Western Diet and the Immune System: An Inflammatory Connection
Christ, A., Lauterbach, M., & Latz, E. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.020 · Cited by 907 · see citing works
Microglia in Alzheimer's disease
Sarlus, H., & Heneka, M. T. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90606 · Cited by 911 · see citing works
Microglia-mediated neuroinflammation in neurodegenerative diseases
Subhramanyam, C. S., Wang, C., Hu, Q., & Dheen, S. T. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.004 · Cited by 875 · see citing works
Scavenger receptors in homeostasis and immunity
Canton, J., Neculai, D., & Grinstein, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3515 · Cited by 838 · see citing works
Immunity in Drosophila melanogaster — from microbial recognition to whole-organism physiology
Buchon, N. S., Silverman, N. S., & Cherry, S. R. (2014) · Nature reviews. Immunology · doi:10.1038/nri3763 · Cited by 868 · see citing works
Regulation of Ligands for the NKG2D Activating Receptor
Raulet, D. H., Gasser, S., Gowen, B. G., Deng, W., & Jung, H. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095951 · Cited by 850 · see citing works
The Role of TLR2 in Infection and Immunity
Nascimento, L. D. O., Massari, P., & Wetzler, L. M. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00079 · Cited by 828 · see citing works
Xu, S., Chaudhary, O., Rodríguez-Morales, P., Sun, X., Chen, D., Zappasodi, R., Xu, Z. Z., Pinto, A. F. M., Williams, A. E., Schulze, I., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.05.003 · Cited by 815 · see citing works
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799 · see citing works
Self-citationMacrophage activation and its role in repair and pathology after spinal cord injury
Gensel, J. C., & Zhang, B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.12.045 · Cited by 774 · see citing works
The blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767 · see citing works
Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling
Płóciennikowska, A., Hromada‐Judycka, A., Borzęcka-Solarz, K., & Kwiatkowska, K. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1762-5 · Cited by 765 · see citing works
The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation
Franklin, B. S., Bossaller, L., De Nardo, D., Ratter, J. M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S. R., Al-Amoudi, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2913 · Cited by 773 · see citing works
Bekkering, S., Quintin, J., Joosten, L. A. B., van der Meer, J. W. M., Netea, M. G., & Riksen, N. P. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303887 · Cited by 735 · see citing works
Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response
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The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · see citing works
Miller, Y. I., Choi, S.-H., Wiesner, P., Fang, L., Harkewicz, R., Hartvigsen, K., Boullier, A., Gonen, A., Diehl, C. J., Que, X., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.223875 · Cited by 654 · see citing works
Rayner, K. J., Sheedy, F. J., Esau, C. C., Hussain, F. N., Temel, R. E., Parathath, S., van Gils, J. M., Rayner, A. J., Chang, A. N., Suarez, Y., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57275 · Cited by 690 · see citing works
Self-citationInflammation in intracerebral hemorrhage: From mechanisms to clinical translation
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Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics
Depuydt, M. A. C., Prange, K. H. M., Slenders, L., Örd, T., Elbersen, D., Boltjes, A., de Jager, S. C. A., Asselbergs, F. W., de Borst, G. J., Aavik, E., et al. (2020) · Circulation Research · doi:10.1161/circresaha.120.316770 · Cited by 590 · see citing works
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Phagocytosis: Receptors, signal integration, and the cytoskeleton
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Yasuda, K., Nakanishi, K., & Tsutsui, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030649 · Cited by 564 · see citing works
Regulation of macrophage immunometabolism in atherosclerosis
Koelwyn, G. J., Corr, E. M., Erbay, E., & Moore, K. J. (2018) · Nature Immunology · doi:10.1038/s41590-018-0113-3 · Cited by 557 · see citing works
Self-citationEndogenous toll‐like receptor ligands and their biological significance
Yu, L., Wang, L., & Chen, S. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01127.x · Cited by 531 · see citing works
DAMPs and DAMP-sensing receptors in inflammation and diseases
Ma, M., Jiang, W., & Zhou, R. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.002 · Cited by 541 · see citing works
Inflammation and its Resolution as Determinants of Acute Coronary Syndromes
Libby, P., Tabas, I. A., Fredman, G., & Fisher, E. A. A. (2014) · Circulation Research · doi:10.1161/circresaha.114.302699 · Cited by 523 · see citing works
Saturated fatty acids trigger TLR4-mediated inflammatory response
Rocha, D. M., Caldas, A. P., Oliveira, L. L., Bressan, J., & Hermsdorff, H. H. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.11.015 · Cited by 492 · see citing works
Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential
Hanke, M. L., & Kielian, T. (2011) · Clinical Science · doi:10.1042/cs20110164 · Cited by 493 · see citing works
The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces
Statovci, D., Aguilera, M., MacSharry, J. A., & Melgar, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00838 · Cited by 490 · see citing works
CD36, a scavenger receptor implicated in atherosclerosis
Park, Y. M. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.38 · Cited by 517 · see citing works
Lucas, K., & Maes, M. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8425-7 · Cited by 466 · see citing works
Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets
Ramji, D. P., & Davies, T. S. (2015) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.04.003 · Cited by 469 · 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
Toll-like receptors: Activation, signalling and transcriptional modulation
Nardo, D. D. (2015) · Cytokine · doi:10.1016/j.cyto.2015.02.025 · Cited by 459 · see citing works
Molecular Biology of Atherosclerosis
Hopkins, P. N. (2013) · Physiological Reviews · doi:10.1152/physrev.00004.2012 · Cited by 456 · see citing works
CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate
Chen, Y., Zhang, J., Cui, W., & Silverstein, R. L. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211314 · Cited by 466 · see citing works
Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain
Shichita, T., Hasegawa, E., Kimura, A., Morita, R., Sakaguchi, R., Takada, I., Sekiya, T., Ooboshi, H., Kitazono, T., Yanagawa, T., et al. (2012) · Nature Medicine · doi:10.1038/nm.2749 · Cited by 455 · see citing works
The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation
Molteni, M., Gemma, S., & Rossetti, C. (2016) · Mediators of Inflammation · doi:10.1155/2016/6978936 · Cited by 456 · see citing works
Microbial modulation of cardiovascular disease
Brown, J. M., & Hazen, S. L. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.149 · Cited by 440 · see citing works
Accessory molecules for Toll-like receptors and their function
Lee, C. C., Avalos, A. M., & Ploegh, H. L. (2012) · Nature reviews. Immunology · doi:10.1038/nri3151 · Cited by 440 · see citing works
Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions
Raggi, P., Genest, J. J., Giles, J. T., Rayner, K. J., Dwivedi, G., Beanlands, R. S., & Gupta, M. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.07.014 · Cited by 434 · see citing works
Self-citationNeuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
NLRP3 inflammasomes link inflammation and metabolic disease
De Nardo, D., & Latz, E. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.05.004 · Cited by 425 · see citing works
Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?
Engelen, S. E., Robinson, A., Zurke, Y.-X., & Monaco, C. G. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00668-4 · Cited by 442 · see citing works
The contribution of neuroinflammation to amyloid toxicity in Alzheimer's disease
Minter, M. R., Taylor, J. M., & Crack, P. J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13411 · Cited by 451 · see citing works
Langelier, C., Kalantar, K. L., Moazed, F., Wilson, M. R., Crawford, E. D., Deiss, T., Belzer, A., Bolourchi, S., Caldera, S., Fung, M., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1809700115 · Cited by 411 · see citing works
Innate sensing of oxidation-specific epitopes in health and disease
Binder, C. J., Papac-Milicevic, N., & Witztum, J. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.63 · Cited by 403 · see citing works
Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier
Tryphena, K. P., Shukla, R., Khatri, D. K., & Vora, L. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102481 · Cited by 417 · see citing works
TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease
Yang, J., Wise, L., & Fukuchi, K.-I. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00724 · Cited by 387 · see citing works
Redox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377 · see citing works
Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease
Maguire, E. M., Pearce, S. W. A., & Xiao, Q. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.08.002 · Cited by 371 · see citing works
IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline
Fu, A. K. Y., Hung, K.-W., Yuen, M. Y. F., Zhou, X., Mak, D. S. Y., Chan, I. C. W., Cheung, T. H., Zhang, B., Fu, W.-Y., Liew, F. Y., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604032113 · Cited by 369 · see citing works
van Gils, J. M., Derby, M. C., Fernandes, L. R., Ramkhelawon, B., Ray, T. D., Rayner, K. J., Parathath, S., Distel, E., Feig, J. L., Alvarez-Leite, J. I., et al. (2012) · Nature Immunology · doi:10.1038/ni.2205 · Cited by 365 · see citing works
Self-citationCD36 tango in cancer: signaling pathways and functions
Wang, J., & Li, Y. (2019) · Theranostics · doi:10.7150/thno.36037 · Cited by 369 · see citing works
Microbial Sensing by Toll-Like Receptors and Intracellular Nucleic Acid SensorsPreprint
Pandey, S., Kawai, T., & Akira, S. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016246 · Cited by 365 · see citing works
Scavenger Receptor Structure and Function in Health and Disease
Abdul‐Zani, I., Stephen, S. L., Mughal, N. A., Russell, D., Homer‐Vanniasinkam, S., Wheatcroft, S. B., & Ponnambalam, S. (2015) · Cells · doi:10.3390/cells4020178 · Cited by 363 · see citing works
A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
Hampel, H., Caraci, F., Cuello, A. C., Caruso, G., Nisticò, R., Corbo, M., Baldacci, F., Toschi, N., Garaci, F., Chiesa, P. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00456 · Cited by 360 · see citing works
Heme on innate immunity and inflammation
Dutra, F. F., & Bozza, M. T. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00115 · Cited by 355 · see citing works
Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis
Bobryshev, Y. V., Ivanova, E. A., Chistiakov, D. A., Nikiforov, N. G., & Orekhov, A. N. (2016) · BioMed Research International · doi:10.1155/2016/9582430 · Cited by 354 · see citing works
DAMPs, MAMPs, and NAMPs in plant innate immunity
Choi, H. W., & Klessig, D. F. (2016) · BMC Plant Biology · doi:10.1186/s12870-016-0921-2 · Cited by 356 · see citing works
Cai, Y., Liu, J., Wang, B., Sun, M., & Yang, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.856376 · Cited by 351 · see citing works
Residual Immune Dysregulation Syndrome in Treated HIV infection
Lederman, M. M., Funderburg, N., Sékaly, R., Klatt, N. R., & Hunt, P. W. (2013) · Advances in immunology · doi:10.1016/b978-0-12-407707-2.00002-3 · Cited by 348 · see citing works
Doens, D., & Fernández, P. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-48 · Cited by 348 · see citing works
Martínez, G. J., Celermajer, D. S., & Patel, S. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.12.027 · Cited by 346 · see citing works
Microglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Astrocytes: Role and Functions in Brain Pathologies
Siracusa, R., Fusco, R., & Cuzzocrea, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01114 · Cited by 342 · see citing works
Innate Immunity and Neurodegeneration
Labzin, L. I., Heneka, M. T., & Latz, E. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104343 · Cited by 319 · see citing works
A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease
PrabhuDas, M., Baldwin, C. L., Bollyky, P. L., Bowdish, D. M. E., Drickamer, K., Febbraio, M., Herz, J., Kobzik, L., Krieger, M., Loike, J. D., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700373 · Cited by 325 · see citing works
Self-citationMicroglia–blood vessel interactions: a double-edged sword in brain pathologies
Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., & Schmidt, M. H. H. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1524-y · Cited by 301 · see citing works
Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer
Watt, M. J., Clark, A. K., Selth, L. A., Haynes, V. R., Lister, N. L., Rebello, R. J., Porter, L. H., Niranjan, B., Whitby, S., Lo, J. C. Y., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau5758 · Cited by 322 · see citing works
Mutant superoxide dismutase 1-induced IL-1β accelerates ALS pathogenesis
Meissner, F., Molawi, K., & Zychlinsky, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002396107 · Cited by 319 · see citing works
Zhao, L., Zhang, C., Luo, X., Wang, P., Zhou, W., Zhong, S., Xie, Y., Jiang, Y., Yang, P., Tang, R., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.04.006 · Cited by 319 · see citing works
Microglia in Health and Disease
Ransohoff, R. M., & Khoury, J. E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020560 · Cited by 303 · see citing works
Self-citationDaniele, S. G., Béraud, D., Davenport, C., Cheng, K., Yin, H., & Maguire-Zeiss, K. A. (2015) · Science Signaling · doi:10.1126/scisignal.2005965 · Cited by 303 · see citing works
The identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
The role of B cells in atherosclerosis
Sage, A. P., Tsiantoulas, D., Binder, C. J., & Mallat, Z. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0106-9 · Cited by 298 · see citing works
B Cells and Humoral Immunity in Atherosclerosis
Tsiantoulas, D., Diehl, C. J., Witztum, J. L., & Binder, C. J. (2014) · Circulation Research · doi:10.1161/circresaha.113.301145 · Cited by 297 · see citing works
- Authors
- Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., Lacy-Hulbert, A., Khoury, J. E., Golenbock, D. T., & Moore, K. J.
- Affiliations
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Washington University in St. Louis (US)
- Corresponding author
- Moore, Kathryn J
- ORCID
- Venue
- Nature Immunology
- Published
- 2009-12-27
- Volume
- 11
- Issue
- 2
- Pages
- 155-161
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2809046
- OpenAlex
- W2045772297
- Cited by
- 1,513
- References
- 42
- Citations by year
- 2026: 53 · 2025: 69 · 2024: 107 · 2023: 74 · 2022: 108 · 2021: 96 · 2020: 102 · 2019: 97 · 2018: 99 · 2017: 94 · 2016: 98 · 2015: 108 · 2014: 81 · 2013: 92 · 2012: 104
- FWCI
- 33.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (068089)
- National Institute on Aging (R01AG20255, R01AG020255, R01AG032349)
- National Institute of Allergy and Infectious Diseases (R01AI079198)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- National Institute of Neurological Disorders and Stroke (R01NS059005)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- CD36, TLR4, TLR6, sterile inflammation, oxidized LDL, amyloid-beta, atherosclerosis, Alzheimer's disease, innate immune activation
- MeSH terms
- Animals, Cell Line, Humans, Inflammation, Lipoproteins, LDL, Mice, Inbred C57BL, Blotting, Western, Signal Transduction, Gene Expression, Amyloid beta-Peptides, Microglia, Mice, Knockout, Chemokines, CD36 Antigens, Reverse Transcriptase Polymerase Chain Reaction, Immunoprecipitation, Atherosclerosis, Toll-Like Receptor 4, Toll-Like Receptor 6, Mice
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