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Innate immune memory in the brain shapes neurological disease hallmarks
Open accessAbstract
Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.
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“Next we tested the effect of Aβ42 and LPS on oxidative stress response in microglial cells as amyloid and inflammation trigger and exacerbate pathological changes in AD brain (Wendeln et al., 2018).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Wendeln et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“peripheral insults that cause a systemic inflammatory response might affect ongoing inflammation in the CNS mainly by microglial activation, production of inflammatory molecules, as well as recruitment of peripheral immune cells into the brain, thus shaping a cerebral inflammatory milieu that may seriously affect neuronal function (50, 52, 53).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [53]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“However, nonspecific microglia activation induced by lipopolysaccharide does not have the same amyloid-promoting effect as myelin dysfunction, as increases, decreases or no changes in amyloid burden have been reported48–51.”
From Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease (2023) · cites this paper as [49]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“A Hif1a epigenetic and transcriptomic signature was recently identified in microglia following immune training by peripheral LPS administration in APP/PS1 mice65.”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [65]
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“Animal and in-vitro studies demonstrate that inflammatory stimuli may initiate long-term priming of the microglia, peripheral CD4+ and CD8+ T cells to a proinflammatory state, (352-354) potentially increasing amyloid plaque deposition.(355)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [355]
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“Our data suggest that PU.1 may contribute to this mechanism of innate immune memory in the brain (Wendeln et al., 2018).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Wendeln et al., 2018
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In the citing paper
“although it is important to note that the efficiency of individual phagocytic processes can be dependent on experimental conditions65–67.”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [65]
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“We found little overlap between the Hif1a module reported in65 and the Hif1a regulon identified here (Supplementary Fig. 13d)”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [65]
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“In healthy mice, peripherally applied LPS can differentially reprogram the epigenome of microglia by inducing either acute immune training or tolerance pending upon the number of injections [102].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [102]
In the citing paper
“and systemic endotoxin precipitates brain pathology in mice expressing prions [74], APP variants [33] or TAU variants [69] or mice with α-synuclein injected in the brain [46].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [33]
In the citing paper
“Microglial markers such as purinergic receptor P2Y G-protein coupled 12 (P2ryl2), transmembrane protein 119 (Tmem119), and Fc receptor-like S, scavenger receptor (Fcrls), are used to define microglia homeostatic state.”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
In the citing paper
“Whereas, inflammatory marker Clec7a is used to define microglia in neurodegenerative state [11].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
In the citing paper
“Immune memory in microglia and macrophages are shaped by epigenetically mediated alterations in the enhancer repertoire of targeted genes [11, 32].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
In the citing paper
“In addition, APP mice with four-time LPS treatment showed increased H3K4me1 levels in putative enhancers related to phagocytic function [11].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
In the citing paper
“Cerebral beta-amyloidosis activates HIF-1a and mTOR pathways, which leads to transcriptional and functional alterations associated with increased inflammatory and immune response genes in MGnD [11].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
In the citing paper
“Peripheral immune stimulation and cerebral beta-amyloidosis can lead to epigenetic modification in microglia.”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
In the citing paper
“These data suggest the differential effect of immune training versus tolerance due to multiple peripheral immune stimulation, which is reflected in the epigenetic landscape of MGnD in AD mouse models.”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [11]
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“Novel nanoparticle technologies (Nance et al., 2017) and new molecular methodologies (Wieghofer et al., 2015) to specifically target microglia have increased our ability to modulate specific signaling pathways in a targeted celltype specific manner.”
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“Such view, in addition to explaining the trouble in decoding microglia role in AD, appears in agreement with the potential effects of innate memory response on microglia phenotype (13), which essentially depend on the previous history of exposure to priming factors in each individual.”
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“Peripheral insults that result in systemic inflammation may facilitate the recruitment of peripheral immune cells to the brain and cause the overactivation of neuroimmune response, leading to neurodegenerative diseases and mood disorders (Cheng et al., 2018; Wendeln et al., 2018; Peng et al., 2022).”
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“Similarly, studies in transgenic AD mouse models revealed that a single dose or short-term application of LPS alone induced an increase in plaque load and a decrease in Aβ uptake 24,36,37 .”
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“…foam cell formation from oxLDL-trained macrophages) and neurodegeneration (such as exacerbation of Alzheimer ’ s pathology by trained microglia (117)) Conversely, endotoxin tolerance can be protective by preventing hyperin fl ammation (as in sepsis), but if excessive it leaves the host…”
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BackgroundLPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils
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“5 mg/kg) gave rise to immune training, while repeated LPS administration of the same dose for four consecutive days produced robust immune tolerance [77].”
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Trained immunity induced by high‐salt diet impedes stroke recovery
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“On a similar note, a single LPS injection was found to induce a trained phenotype of murine microglia; this in turn, promoted the neuropathology in a model of Alzheimer’s disease, increasing both amyloid-b levels and the plaque load, and augmented IL-1b levels after brain ischaemia (71).”
BackgroundNLRP3 Exacerbate NETosis-Associated Neuroinflammation in an LPS-Induced Inflamed Brain
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BackgroundMetabolic Endotoxemia: From the Gut to Neurodegeneration
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“In an Alzheimer ’ s disease mouse model, immune training exacerbates b -amyloid deposition, while tolerance attenuates it (188).”
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“In addition, microglia have recently been shown to become epigenetically modified in response to peripheral inflammatory stimuli, thus affecting their reaction to additional insults for up to 6 mo (56).”
BackgroundBromodomain inhibitor I‐BET151 suppresses immune responses during fungal–immune interaction
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“Similarly, brain-resident macrophages (microglia) can build a long-term proinflammatory phenotype after brief peripheral inflammatory stimuli, which persists for at least 6 months [38].”
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Genome-Wide Screen and Validation of Microglia Pro-Inflammatory Mediators in Stroke
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“Along these lines, innate immune memory manipulation may improve AD outcome by de-escalating microglia via peripherallyapplied tolerizing stimuli (13).”
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“In the APP23 transgenic mouse model of AD, it was demonstrated that peripheral stimuli could train microglia cells in the brain to develop innate immune memory, which in turn exacerbated β -amyloidosis [91].”
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“‘trained’ or ‘tolerant’ to toxins like LPS [27].”
BackgroundRapamycin Modulates the Proinflammatory Memory-Like Response of Microglia Induced by BAFF
Wang, J., Yang, C., Hou, X., Xu, J., Yang, Y., Qin, L., & Yang, P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.639049 · Cited by 30
“confirmed that microglia could be prepared to confer long-lasting memory (5).”
BackgroundResultInfluentialHonokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming
Li, W., Wang, S., Zhang, H., Li, B., Xu, L., Li, Y., Kong, C., Jiao, H., Wang, Y., Pang, Y., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210177 · Cited by 31
Yang, Y., García-Cruzado, M., Zeng, H., Camprubí-Ferrer, L., Bahatyrevich-Kharitonik, B., Bachiller, S., & Deierborg, T. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.07.006 · Cited by 31
“Thus, IIM can suppress or enhance the immune responses to a secondary inflammatory stimulus (Wendeln et al., 2018; Neher and Cunningham, 2019).”
BackgroundResultInfluentialLiang, N., Nho, K. T., Newman, J. W. I., Arnold, M., Huynh, K., Meikle, P. J., Borkowski, K., Kaddurah‐Daouk, R., Kueider‐Paisley, A., Doraiswamy, P. M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-67177-5 · Cited by 37
“As results, peripheral inflammation stimuli can modulate the expression of inflammation-related genes in the brain 19 and exacerbate CNS neurodegeneration 53 .”
BackgroundMicroglia Sing the Prelude of Neuroinflammation-Associated Depression
Li, Q., Xie, Y., Lin, J., Li, M., Gu, Z., Xin, T., Zhang, Y., Lu, Q., Guo, Y., Xing, Y., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04575-w · Cited by 30
“Upon subsequent immune stimulation, microglia exhibit immune memory, which triggers the secretion of a greater quantity of pro-inflammatory cytokines [179].”
Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities
Liu, Y., Wu, L., Peng, W., & Mao, X. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102638 · Cited by 32
Bindu, S., Dandapat, S., Manikandan, R., Dinesh, M., Anbazhagan, S., Pashupathi, M., Dhawan, M. K., Tiwari, R., Bilal, M., Emran, T. B., et al. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2040238 · Cited by 32
“Modifications in H3K4me1 and H3K27ac that persist up to 6 months may elicit immune training in neural macrophages.(49) In another study, similar observations were found in microglia, demonstrating that histone acetyltransferases HDAC1/2 are required for this process.”
ResultKaneko, R., Matsui, A., Watanabe, M., Harada, Y., Kanamori, M., Awata, N., Kawazoe, M., Takao, T., Kobayashi, Y., Kikutake, C., et al. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00257-7 · Cited by 30
“In a mouse model of Alzheimer’s disease, immune training with a single dose of LPS exacerbates amyloid-beta accumulation in the brain, while immune tolerance with continuous intraperitoneal administration of LPS alleviates it [32].”
BackgroundAdulthood systemic inflammation accelerates the trajectory of age-related cognitive decline
Barter, J., Kumar, A., Bean, L. A., Ciesla, M. R., & Foster, T. C. (2021) · Aging · doi:10.18632/aging.203588 · Cited by 29
“In contrast, repeated LPS injections induce immune tolerance of microglia, which can be detected weeks or months following LPS injections [30, 31].”
Backgroundde Toledo, J. H. D. S., Fraga‐Silva, T. F. D. C., Borim, P. A., de Oliveira, L. R. C., Oliveira, E. D. S., Périco, L. L., Hiruma-Lima, C. A., de Souza, A. A. L., de Oliveira, C. A. F., Padilha, P. D. M., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.571844 · Cited by 33
Epigenetic gene expression links heart failure to memory impairment
Islam, R., Lbik, D., Sakib, M. S., Hofmann, R. M., Berulava, T., Jiménez‐Mausbach, M., Cha, J., Goldberg, M., Vakhtang, E., Schiffmann, C., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.201911900 · Cited by 29
Self-citationDevelopmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
Carloni, E., Ramos, A., & Hayes, L. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313035 · Cited by 30
“As far as we are aware, few studies have systematically addressed the epigenetic regulation of training and tolerance in microglia using preclinical models of aging and neurodegenerative diseases [134,169].”
BackgroundInfluentialThomas, S. D., Abdalla, S., Eissa, N., Akour, A. A., Jha, N. K., Ojha, S. K., & Sadek, B. S. (2024) · Pharmaceuticals · doi:10.3390/ph17070831 · Cited by 33
“This immune memory may play a role in modulating various neurological pathologies and shed light on the dual role of histamine [115].”
BackgroundDenstaedt, S. J., Spencer-Segal, J. L., Newstead, M. W., Laborc, K. F., Zeng, X., Standiford, T. J., & Singer, B. H. (2019) · Shock · doi:10.1097/shk.0000000000001435 · Cited by 28
Behavioral adaptations in a relapsing mouse model of colitis
Matisz, C. E., Vicentini, F., Hirota, S. A., Sharkey, K. A., & Gruber, A. J. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.112802 · Cited by 26
Glycoengineering artificial receptors for microglia to phagocytose Aβ aggregates
Yu, D., Liu, C., Zhang, H., Ren, J., & Qu, X. (2021) · Chemical Science · doi:10.1039/d0sc07067j · Cited by 28
Microtubule acetylation: A reading key to neural physiology and degeneration
Cappelletti, G., Calogero, A. M., & Rolando, C. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135900 · Cited by 29
Innate immune activation: Parallels in alcohol use disorder and Alzheimer’s disease
Ramos, A., Joshi, R., & Szabó, G. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.910298 · Cited by 29
“In addition, stimulation of TLR4 in microglia modulates the cell’s capacity to engulf Aβ plaques and subsequently affect disease progression (Wendeln et al., 2018).”
BackgroundAl, B., Suen, T. K., Placek, K., & Netea, M. G. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.06.014 · Cited by 31
Choreño-Parra, J. A., Islas-Weinstein, L., Yunis, E. J., Zúñiga, J., & Hernández‐Pando, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00226 · Cited by 29
Guerrero‐Carrasco, M., Targett, I. L., Olmos‐Alonso, A., Vargas‐Caballero, M., & Gómez‐Nicola, D. (2024) · Glia · doi:10.1002/glia.24532 · Cited by 27
Mertens, R. T., Misra, A., Xiao, P., Baek, S., Rone, J. M., Mangani, D., Sivanathan, K. N., Arojojoye, A. S., Awuah, S. G., Lee, I., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.06.001 · Cited by 27
A dynamic and multimodal framework to define microglial states
Sankowski, R., & Prinz, M. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01978-3 · Cited by 31
“Epigenetic marks from earlier immunological events shape subsequent responses 60,67 .”
Self-citationMetabolic regulation of immune memory and function of microglia
Nirakis, N., Dimothyra, S., Karadima, E., & Alexaki, V. I. (2025) · eLife · doi:10.7554/elife.107552 · Cited by 26
“Systemic administration of lipopolysaccharide (LPS) is widely used to prime microglia in mice ( Wendeln et al., 2018 ; Alexaki, 2021 ; Alexaki et al., 2018 ).”
InfluentialInfectious and lifestyle modifiers of immunity and host resilience
Bajpai, G., & Nahrendorf, M. (2021) · Immunity · doi:10.1016/j.immuni.2021.05.011 · Cited by 27
Karczewski, J., Zielińska, A., Staszewski, R., Eder, P., Dobrowolska, A., & Souto, E. B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116145 · Cited by 27
“Infectious agents might also modulate the innate immune cells via epigenetic modifications, increasing the risk of neurodegenerative disorders [47].”
BackgroundHermanns, N., Wroblewski, V., Bascuñana, P., Wolf, B., Polyák, A., Roß, T. L., Bengel, F. M., & Thackeray, J. T. (2022) · Basic Research in Cardiology · doi:10.1007/s00395-022-00961-4 · Cited by 27
“endothelin-1 (ET-1) to the cortical parenchyma (n = 23) [43].”
BackgroundMethodInfluentialMicroglia–neuron–vascular interactions in ischemia
Lénárt, N., Cserép, C., Császár, E., Pósfai, B., & Dénes, Á. (2023) · Glia · doi:10.1002/glia.24487 · Cited by 28
“Even a single, acute systemic inflammatory stimulus results in marked, long-lasting changes in microglial phenotypes and inflammatory responses via epigenetic reprogramming (Wendeln et al., 2018).”
BackgroundChouhan, J. K., Püntener, U., Booth, S. G., & Teeling, J. L. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.760721 · Cited by 24
“These experiments have yielded conflicting results that seem to depend on dose, timing, and frequency of LPS administration (Wendeln et al., 2018; Tejera et al., 2019).”
How the gut microbiota impacts neurodegenerative diseases by modulating CNS immune cells
Schaible, P., Henschel, J., & Erny, D. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03371-0 · Cited by 32
“In contrast, sequential low-dose LPS stimulation can induce immune memory in microglia cells, causing a tolerance effect [178].”
Fernández‐Arjona, M. D. M., León‐Rodríguez, A., Grondona, J. M., & López-Ávalos, M. D. (2022) · Glia · doi:10.1002/glia.24217 · Cited by 28
“…which has gained interest after evidences pointing that it might be underneath neurodegeneration, cognitive impairment and behavioral disturbances (De Sousa et al., 2021; Frank et al., 2020; Lisboa et al., 2016; Norden et al., 2015; Perry & Holmes, 2014; Wendeln et al., 2018; Yirmiya et al., 2015).”
BackgroundWang, Y., Hu, Z., Liu, H., Gu, Y., Ye, M., Lu, Q., Lu, X., & Huang, C. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.06.015 · Cited by 26
Onisiforou, A., & Spyrou, G. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.843128 · Cited by 25
“In a mouse model of AD, it was shown that application of a peripheral stimuli caused innate immune memory training of microglia cells in the brain which exacerbated b amyloidosis, whereas innate immune tolerance alleviated this effect (95).”
BackgroundSchwabenland, M., Mossad, O., Sievert, A., Peres, A. G., Ringel, E., Baasch, S., Kolter, J., Cascone, G., Dokalis, N., Vlachos, A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38373-0 · Cited by 26
“In our present work, early immune activation resulted in epigenetically-modi fi ed microglia, which is in accordance with previous data from our and other groups indicating that acetylation and methylation of H3 are associated with altered microglial function after an immune challenge 69,70 .”
Self-citationNeuro-Immuno-Gene- and Genome-Editing-Therapy for Alzheimer’s Disease: Are We There Yet?
Raikwar, S. P., Thangavel, R., Dubova, I., Ahmed, M. E., Selvakumar, G. P., Kempuraj, D., Zaheer, S. A., Iyer, S. S., & Zaheer, A. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180422 · Cited by 27
“We are cautiously optimistic that, multi-faceted approaches simultaneously targeting neuroinflammation [117, 155, 156], blood-brain barrier [157, 158], robust A processing and clearance by targeted immunotherapies [13], tau phosphorylation [159], APOE4 [160–164], improving mitochondrial function [165–167], iPS cell-ba…”
BackgroundRelB controls adaptive responses of astrocytes during sterile inflammation
Gupta, A. S., Waters, M. R., Biswas, D. D., Brown, L. N., Surace, M. J., Floros, C., Siebenlist, U. K., & Kordula, T. (2019) · Glia · doi:10.1002/glia.23619 · Cited by 28
“, 2007), tolerance has only recently been found to exist in the resident innate immune cells of the brain, microglia (Schaafsma et al., 2015; Wendeln et al., 2018).”
BackgroundMethodInfluentialDialysis and cognitive impairment
McIntyre, C. W., & Jain, A. (2025) · Nature Reviews Nephrology · doi:10.1038/s41581-025-00960-3 · Cited by 31
“In animal models, endotoxin exposure can significantly worsen ischaemic brain injury following a vascular insult 88 .”
Lee, J., Cho, W., Yu, J., & Hyun, Y. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03468-6 · Cited by 26
“To achieve maximum NLRP3 activation in the brain, WT mice were injected with LPS (0.8 mg/kg/day) at 24 h intervals for 2 days [57].”
InfluentialZhao, X., Yu, J., Xu, B., Xu, Z., Lei, X., Han, S., Luo, S., Zhang, C. M., Peng, G., Li, J., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70331 · Cited by 27
“44,15 Therefore, this study focused on bEVs carrying LPS and found that theseLPS-containingbEVscoulddirectlypenetratetheBBB.”
Nutritional Modulation of Innate Immunity: The Fat–Bile–Gut Connection
Chèvre, R., Silvestre-Roig, C., & Soehnlein, O. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.08.002 · Cited by 24
Long‐term risk of dementia following hospitalization due to physical diseases: A multicohort study
Sipilä, P. N., Lindbohm, J. V., Singh‐Manoux, A., Shipley, M. J., Kiiskinen, T., Havulinna, A. S., Vahtera, J., Nyberg, S. T., Pentti, J., & Mika Kivimaki, B. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12167 · Cited by 24
Intestinal Flora Composition Determines Microglia Activation and Improves Epileptic Episode Progress
Ding, X., Zhou, J., Zhao, L., Chen, M., Wang, S., Zhang, M., Zhang, X., & Jiang, G. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.835217 · Cited by 25
“The central nervous system has been shown to respond to environmental changes in immune status induced via the peripheral administration of lipopolysaccharide (LPS), which can result in immune training or immune tolerance in the brain immune system (Wendeln et al., 2018).”
BackgroundSrinivasan, M., & Walker, C. L. (2022) · ASN NEURO · doi:10.1177/17590914221120190 · Cited by 25
“…of the interdependent relationship between the circadian rhythm of clock genes, GC and NF-κB signaling sensitizes the brain to chronic inflammatory challenges and associated pathologies (de Kloet et al., 2018; Liu et al., 2016; Sochocka et al., 2017; Tarr et al., 2014; Wendeln et al., 2018).”
BackgroundMaurya, S. K., Gupta, S., & Mishra, R. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1072046 · Cited by 26
Pathological roles of macrophages in Leishmania infections
Goto, Y., & Mizobuchi, H. (2023) · Parasitology International · doi:10.1016/j.parint.2023.102738 · Cited by 29
Lü, Y., Girardi, C. S., Fitz, N. F., McGuire, M. R., Ostach, M. A., Mamun-Or-Rashid, A. N. M., Lefterov, I. M., & Koldamova, R. P. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112785 · Cited by 27
Microglia Reactivity: Heterogeneous Pathological Phenotypes
Hirbec, H., Rassendren, F., & Audinat, É. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9658-2_4 · Cited by 24
Back to the origins: Human brain organoids to investigate neurodegeneration
Faravelli, I., Costamagna, G., Tamanini, S., & Corti, S. (2020) · Brain Research · doi:10.1016/j.brainres.2019.146561 · Cited by 25
TREM2 regulates microglial phagocytosis of synapses in innate immune tolerance
Meng, J., Han, L., Xu, H., Zhang, L., Liu, Z., Zhou, Y., Zhang, X., Luo, H., & Zhang, Y. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111445 · Cited by 25
Hoffmann, M. H., Kirchner, H., Krönke, G., Riemekasten, G., & Bonelli, M. M. (2024) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2023-224092 · Cited by 25
Metadata
- Authors
- Wendeln, A.-C., Degenhardt, K., Kaurani, L., Gertig, M., Ulas, T., Jain, G., Wagner, J., Häsler, L. M., Wild, K., Skodras, A., Blank, T., Staszewski, O., Datta, M., Centeno, T. P., Capece, V., Islam, M. R., Kerimoglu, C., Staufenbiel, M., Schultze, J. L., Beyer, M., Prinz, M., Jucker, M., Fischer, A., & Neher, J. J.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- University of Bonn (DE)
- University of Freiburg (DE)
- Corresponding author
- Neher, Jonas J.
- ORCID
- Venue
- Nature
- Published
- 2018-04
- Volume
- 556
- Issue
- 7701
- Pages
- 332-338
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6038912
- OpenAlex
- W2796983933
- Cited by
- 956
- References
- 51
- Citations by year
- 2026: 117 · 2025: 102 · 2024: 120 · 2023: 106 · 2022: 121 · 2021: 135 · 2020: 104 · 2019: 90 · 2018: 60
- FWCI
- 43.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DZNE Pub (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- trained immunity, immunological imprinting, immune tolerance, microglia, epigenetic reprogramming, neuroinflammation, Alzheimer's disease, beta-amyloidosis, stroke, neuropathology
- MeSH terms
- Alzheimer Disease, Amyloidosis, Animals, Brain, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Immune Tolerance, Immunity, Innate, Immunologic Memory, Inflammation, Male, Nervous System Diseases, Microglia, Stroke, Epigenesis, Genetic, Mice
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