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1

Arneth, Borros. "Trained innate immunity." Immunologic Research 69, no. 1 (2021): 1–7. http://dx.doi.org/10.1007/s12026-021-09170-y.

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Bird, Lucy. "Targeting trained immunity." Nature Reviews Immunology 19, no. 1 (2018): 2–3. http://dx.doi.org/10.1038/s41577-018-0097-0.

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Cortes-Perez, Naima G., Alejandra de Moreno de de Moreno de LeBlanc, Jorge G. Gomez-Gutierrez, Jean Guy LeBlanc, and Luis G. Bermúdez-Humarán. "Probiotics and Trained Immunity." Biomolecules 11, no. 10 (2021): 1402. http://dx.doi.org/10.3390/biom11101402.

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The characteristics of innate immunity have recently been investigated in depth in several research articles, and original findings suggest that innate immunity also has a memory capacity, which has been named “trained immunity”. This notion has revolutionized our knowledge of the innate immune response. Thus, stimulation of trained immunity represents a therapeutic alternative that is worth exploring. In this context, probiotics, live microorganisms which when administered in adequate amounts confer a health benefit on the host, represent attractive candidates for the stimulation of trained i
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Jauregui, Paula. "Trained immunity across organs." Nature Immunology 25, no. 9 (2024): 1509. http://dx.doi.org/10.1038/s41590-024-01958-y.

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5

van der Heijden, Charlotte D. C. C., Marlies P. Noz, Leo A. B. Joosten, Mihai G. Netea, Niels P. Riksen, and Samuel T. Keating. "Epigenetics and Trained Immunity." Antioxidants & Redox Signaling 29, no. 11 (2018): 1023–40. http://dx.doi.org/10.1089/ars.2017.7310.

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6

Bird, Lucy. "Trained immunity by HSCs." Nature Reviews Immunology 20, no. 5 (2020): 276–77. http://dx.doi.org/10.1038/s41577-020-0299-0.

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7

Bekkering, Siroon, Jorge Domínguez-Andrés, Leo A. B. Joosten, Niels P. Riksen, and Mihai G. Netea. "Trained Immunity: Reprogramming Innate Immunity in Health and Disease." Annual Review of Immunology 39, no. 1 (2021): 667–93. http://dx.doi.org/10.1146/annurev-immunol-102119-073855.

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Traditionally, the innate and adaptive immune systems are differentiated by their specificity and memory capacity. In recent years, however, this paradigm has shifted: Cells of the innate immune system appear to be able to gain memory characteristics after transient stimulation, resulting in an enhanced response upon secondary challenge. This phenomenon has been called trained immunity. Trained immunity is characterized by nonspecific increased responsiveness, mediated via extensive metabolic and epigenetic reprogramming. Trained immunity explains the heterologous effects of vaccines, which re
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Velikova, Tsvetelina, Issa El Kaouri, Konstantina Bakopoulou, et al. "Mucosal Immunity and Trained Innate Immunity of the Gut." Gastroenterology Insights 15, no. 3 (2024): 661–75. http://dx.doi.org/10.3390/gastroent15030048.

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Mucosal immunity and trained innate immunity of the gut play a pivotal role in maintaining intestinal homeostasis and defending against microbial pathogens. This review provides an overview of the mechanisms underlying mucosal immunity and the concept of trained innate immunity in the gut. We discuss the interaction between gut microbiota and the host immune system, highlighting the role of epithelial cells, dendritic cells, and innate lymphoid cells, as well as the novel concept of trained innate immunity and its role in perpetuating or attenuating gut inflammation. We also comment on the cur
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9

Hanb, Chaofeng. "Metabolic basis of trained immunity." American Journal of Biomedical Science & Research 4, no. 2 (2019): 62–64. http://dx.doi.org/10.34297/ajbsr.2019.04.000762.

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10

Geckin, Büsranur, Friedrich Konstantin Föhse, Jorge Domínguez-Andrés, and Mihai G. Netea. "Trained immunity: implications for vaccination." Current Opinion in Immunology 77 (August 2022): 102190. http://dx.doi.org/10.1016/j.coi.2022.102190.

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11

Merriman, Tony R., and Leo A. B. Joosten. "CHIP and gout: trained immunity?" Blood 140, no. 10 (2022): 1054–56. http://dx.doi.org/10.1182/blood.2022017212.

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12

Bekkering, Siroon, Leo A. B. Joosten, Jos W. M. van der Meer, Mihai G. Netea, and Niels P. Riksen. "Trained innate immunity and atherosclerosis." Current Opinion in Lipidology 24, no. 6 (2013): 487–92. http://dx.doi.org/10.1097/mol.0000000000000023.

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13

Ochando, Jordi, Zahi A. Fayad, Joren C. Madsen, Mihai G. Netea, and Willem J. M. Mulder. "Trained immunity in organ transplantation." American Journal of Transplantation 20, no. 1 (2019): 10–18. http://dx.doi.org/10.1111/ajt.15620.

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14

Arts, Rob J. W., Leo A. B. Joosten, and Mihai G. Netea. "Immunometabolic circuits in trained immunity." Seminars in Immunology 28, no. 5 (2016): 425–30. http://dx.doi.org/10.1016/j.smim.2016.09.002.

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15

Bekkering, S., J. Quintin, L. A. B. Joosten, J. W. M. van der Meer, M. G. Netea, and N. P. Riksen. "Trained Innate Immunity and Atherosclerosis." Clinical Therapeutics 36, no. 8 (2014): e3. http://dx.doi.org/10.1016/j.clinthera.2014.05.016.

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16

Mulder, Willem J. M., Jordi Ochando, Leo A. B. Joosten, Zahi A. Fayad, and Mihai G. Netea. "Therapeutic targeting of trained immunity." Nature Reviews Drug Discovery 18, no. 7 (2019): 553–66. http://dx.doi.org/10.1038/s41573-019-0025-4.

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17

York, Ashley. "M. tuberculosis stifles trained immunity." Nature Reviews Microbiology 19, no. 1 (2020): 2. http://dx.doi.org/10.1038/s41579-020-00479-3.

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18

Bossu’, Paola, Laura Sireno, Micaela Lembo, and Elisa Toppi. "Trained Immunity in Neurodegenerative Diseases." Journal of Immunology 208, no. 1_Supplement (2022): 163.03. http://dx.doi.org/10.4049/jimmunol.208.supp.163.03.

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Abstract Alzheimer’s disease (AD) and Parkinson’s disease (PD) are complex and progressive neurodegenerative disturbances leading to cognitive or motor dysfunctions and lacking effective therapy. A deregulation of innate immune response and inflammation appears to be deeply involved in both illnesses, though with still unclear mechanisms. Evidence in animals attributes a neurodegeneration-modulating role to mechanisms of innate memory, but human data on this topic are still scarce. In this study, we investigated whether -possibly due to concomitant factors including enhanced infectious burden,
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19

Viola, Maria Francesca, and Elvira Mass. "Bacterial translocation promotes trained immunity." Immunity 58, no. 2 (2025): 268–70. https://doi.org/10.1016/j.immuni.2025.01.011.

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20

Vetvicka, Vaclav, Petr Sima, and Luca Vannucci. "Trained Immunity as an Adaptive Branch of Innate Immunity." International Journal of Molecular Sciences 22, no. 19 (2021): 10684. http://dx.doi.org/10.3390/ijms221910684.

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The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as
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21

Dore, Maria Pina, and Giovanni Mario Pes. "Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection." International Journal of Molecular Sciences 25, no. 11 (2024): 5856. http://dx.doi.org/10.3390/ijms25115856.

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Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that rep
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22

Koeken, Valerie A. C. M., Reinout Crevel, Mihai G. Netea, and Yang Li. "Resolving trained immunity with systems biology." European Journal of Immunology 51, no. 4 (2021): 773–84. http://dx.doi.org/10.1002/eji.202048882.

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23

Lim, Gregory B. "Hyperglycaemia-induced trained immunity promotes atherosclerosis." Nature Reviews Cardiology 18, no. 10 (2021): 687. http://dx.doi.org/10.1038/s41569-021-00606-4.

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24

Stevens, W. B. C., M. G. Netea, A. P. Kater, and W. J. F. M. van der Velden. "'Trained immunity: consequences for lymphoid malignancies." Haematologica 101, no. 12 (2016): 1460–68. http://dx.doi.org/10.3324/haematol.2016.149252.

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25

Włodarczyk, Marcin, Magdalena Druszczyńska, and Marek Fol. "Trained Innate Immunity Not Always Amicable." International Journal of Molecular Sciences 20, no. 10 (2019): 2565. http://dx.doi.org/10.3390/ijms20102565.

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The concept of “trained innate immunity” is understood as the ability of innate immune cells to remember invading agents and to respond nonspecifically to reinfection with increased strength. Trained immunity is orchestrated by epigenetic modifications leading to changes in gene expression and cell physiology. Although this phenomenon was originally seen mainly as a beneficial effect, since it confers broad immunological protection, enhanced immune response of reprogrammed innate immune cells might result in the development or persistence of chronic metabolic, autoimmune or neuroinfalmmatory d
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26

Thiem, Kathrin, Rinke Stienstra, Niels P. Riksen, and Samuel T. Keating. "Trained immunity and diabetic vascular disease." Clinical Science 133, no. 2 (2019): 195–203. http://dx.doi.org/10.1042/cs20180905.

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Abstract Trained immunity is a recently described phenomenon whereby innate immune cells undergo functional reprogramming in response to microbial products, vaccines, or other stimuli, leading them to mount a sensitized nonspecific response to subsequent stimulation. While it is essential for the host response to pathogens, many diseases are the product of excessive or chronic inflammation. Atherosclerosis is a disease characterized by chronic low-grade inflammation of the arterial wall leading to plaque formation, where macrophages are the most abundant cell regulating plaque progression and
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27

Sohrabi, Yahya, Rinesh Godfrey, and Hannes M. Findeisen. "Altered Cellular Metabolism Drives Trained Immunity." Trends in Endocrinology & Metabolism 29, no. 9 (2018): 602–5. http://dx.doi.org/10.1016/j.tem.2018.03.012.

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28

Riksen, Niels P. "Trained immunity and atherosclerotic cardiovascular disease." Current Opinion in Lipidology 30, no. 5 (2019): 395–400. http://dx.doi.org/10.1097/mol.0000000000000628.

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29

Ferreira, Anaisa V., Valerie A. C. M. Koeken, Vasiliki Matzaraki, et al. "Glutathione Metabolism Contributes to the Induction of Trained Immunity." Cells 10, no. 5 (2021): 971. http://dx.doi.org/10.3390/cells10050971.

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The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has been associated with the trained immunity phenotype, we hypothesized that the increased ROS levels and the main intracellular redox molecule glutathione play a role in the induction of trained immunity. Here we show that pharmacological inhibition of ROS in an in vitro model of trained immunity did n
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30

Ciarlo, Eleonora, Tytti Heinonen, Charlotte Théroude, et al. "Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections." Journal of Infectious Diseases 222, no. 11 (2019): 1869–81. http://dx.doi.org/10.1093/infdis/jiz692.

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Abstract Background The innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections. Methods Mice were trained and subjected to systemic infections, peritonitis, enteritis, and pneumonia induced by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Cit
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31

Koeken, Valerie A. C. M., Cancan Qi, Vera P. Mourits, et al. "Plasma metabolome predicts trained immunity responses after antituberculosis BCG vaccination." PLOS Biology 20, no. 9 (2022): e3001765. http://dx.doi.org/10.1371/journal.pbio.3001765.

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The antituberculosis vaccine Bacillus Calmette–Guérin (BCG) induces nonspecific protection against heterologous infections, at least partly through induction of innate immune memory (trained immunity). The amplitude of the response to BCG is variable, but the factors that influence this response are poorly understood. Metabolites, either released by cells or absorbed from the gut, are known to influence immune responses, but whether they impact BCG responses is not known. We vaccinated 325 healthy individuals with BCG, and collected blood before, 2 weeks and 3 months after vaccination, to asse
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32

van Puffelen, Jelmer H., Boris Novakovic, Liesbeth van Emst, et al. "Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections." Journal for ImmunoTherapy of Cancer 11, no. 1 (2023): e005518. http://dx.doi.org/10.1136/jitc-2022-005518.

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BackgroundBCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.MethodsThe aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine product
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33

Zhang, Chen, Jie Yin, Jian Zheng, et al. "EZH2 identifies the precursors of human natural killer cells with trained immunity." Cancer Biology & Medicine 18, no. 4 (2021): 1021–39. http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0791.

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Objective: Trained immunity of natural killer (NK) cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation. However, the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown. We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12, IL-15, and IL-18, and that an NK cell subset might exist that is mainly responsible for the induction of trained immunit
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34

Groh, Laszlo, Mihai G. Netea, Niels P. Riksen, and Samuel T. Keating. "Getting to the marrow of trained immunity." Epigenomics 10, no. 9 (2018): 1151–54. http://dx.doi.org/10.2217/epi-2018-0098.

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35

Badii, Medeea, Orsolya Gaal, Radu A. Popp, Tania O. Crișan, and Leo A. B. Joosten. "Trained immunity and inflammation in rheumatic diseases." Joint Bone Spine 89, no. 4 (2022): 105364. http://dx.doi.org/10.1016/j.jbspin.2022.105364.

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36

Muñoz-Wolf, Natalia, and Ed C. Lavelle. "Promotion of trained innate immunity by nanoparticles." Seminars in Immunology 56 (August 2021): 101542. http://dx.doi.org/10.1016/j.smim.2021.101542.

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37

Choudhury, Robin P., Laurienne Edgar, Mikael Rydén, and Edward A. Fisher. "Diabetes and Metabolic Drivers of Trained Immunity." Arteriosclerosis, Thrombosis, and Vascular Biology 41, no. 4 (2021): 1284–90. http://dx.doi.org/10.1161/atvbaha.120.314211.

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Accumulating evidence shows how diverse physiological functions, such as metabolism, immunity, tissue homeostasis, and hematopoiesis, are intricately and profoundly intertwined at multiple levels. This brief review will present evidence from a rapidly expanding field of immunometabolism, highlighting how cells that are relevant to processes at play in determining vascular health and disease can be programmed by changes in their metabolic environment. It will focus on how such changes can be imprinted or trained, particularly through epigenetic modifications, such that adaptations driven by met
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Angulo, Miriam, and Carlos Angulo. "Trained immunity against diseases in domestic animals." Acta Tropica 229 (May 2022): 106361. http://dx.doi.org/10.1016/j.actatropica.2022.106361.

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39

Mantovani, Alberto, and Mihai G. Netea. "Trained Innate Immunity, Epigenetics, and Covid-19." New England Journal of Medicine 383, no. 11 (2020): 1078–80. http://dx.doi.org/10.1056/nejmcibr2011679.

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40

Roy, Suvra, Peter Bossier, Parisa Norouzitallab, and Daisy Vanrompay. "Trained immunity and perspectives for shrimp aquaculture." Reviews in Aquaculture 12, no. 4 (2020): 2351–70. http://dx.doi.org/10.1111/raq.12438.

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41

Román, Patricia Conde-San, Mounia S. Braza, and Jordi C. Ochando. "Targeting Trained Immunity Promotes Organ Transplant Acceptance." Transplantation 102 (July 2018): S693. http://dx.doi.org/10.1097/01.tp.0000543647.76941.31.

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42

Gyssens, I. C., and M. G. Netea. "Heterologous effects of vaccination and trained immunity." Clinical Microbiology and Infection 25, no. 12 (2019): 1457–58. http://dx.doi.org/10.1016/j.cmi.2019.05.024.

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43

Netea, Mihai G., and Jos W. M. van der Meer. "Trained Immunity: An Ancient Way of Remembering." Cell Host & Microbe 21, no. 3 (2017): 297–300. http://dx.doi.org/10.1016/j.chom.2017.02.003.

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44

Arts, Rob J. W., Agostinho Carvalho, Claudia La Rocca, et al. "Immunometabolic Pathways in BCG-Induced Trained Immunity." Cell Reports 17, no. 10 (2016): 2562–71. http://dx.doi.org/10.1016/j.celrep.2016.11.011.

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45

Mourits, Vera P., Jac CHM Wijkmans, Leo AB Joosten, and Mihai G. Netea. "Trained immunity as a novel therapeutic strategy." Current Opinion in Pharmacology 41 (August 2018): 52–58. http://dx.doi.org/10.1016/j.coph.2018.04.007.

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46

Tercan, Helin, Niels P. Riksen, Leo A. B. Joosten, Mihai G. Netea, and Siroon Bekkering. "Trained Immunity." Arteriosclerosis, Thrombosis, and Vascular Biology, October 22, 2020. http://dx.doi.org/10.1161/atvbaha.120.314212.

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Adaptive immune responses are characterized by antigen specificity and induction of lifelong immunologic memory. Recently, it has been reported that innate immune cells can also build immune memory characteristics—a process termed trained immunity. Trained immunity describes the persistent hyperresponsive phenotype that innate immune cells can develop after brief stimulation. Pathogenic stimuli such as microorganisms, and also endogenous molecules including uric acid, oxidized LDL (low-density lipoprotein), and catecholamines, are capable of inducing memory in monocytes and macrophages. While
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47

De Zuani, Marco, and Jan Frič. "Train the Trainer: Hematopoietic Stem Cell Control of Trained Immunity." Frontiers in Immunology 13 (January 27, 2022). http://dx.doi.org/10.3389/fimmu.2022.827250.

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Recent evidence shows that innate immune cells, in addition to B and T cells, can retain immunological memory of their encounters and afford long-term resistance against infections in a process known as ‘trained immunity’. However, the duration of the unspecific protection observed in vivo is poorly compatible with the average lifespan of innate immune cells, suggesting the involvement of long-lived cells. Accordingly, recent studies demonstrate that hematopoietic stem and progenitor cells (HSPCs) lay at the foundation of trained immunity, retaining immunological memory of infections and givin
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Martín‐Cruz, Leticia, Carmen Sevilla‐Ortega, Alba Angelina, et al. "From trained immunity in allergy to trained immunity‐based allergen vaccines." Clinical & Experimental Allergy, December 9, 2022. http://dx.doi.org/10.1111/cea.14261.

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Sviridov, Dmitri, Yury I. Miller, and Michael I. Bukrinsky. "Trained Immunity and HIV Infection." Frontiers in Immunology 13 (July 8, 2022). http://dx.doi.org/10.3389/fimmu.2022.903884.

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Findings that certain infections induce immunity not only against the causing agent, but also against an unrelated pathogen have intrigued investigators for many years. Recently, underlying mechanisms of this phenomenon have started to come to light. It was found that the key cells responsible for heterologous protection are innate immune cells such as natural killer cells (NKs), dendritic cells, and monocytes/macrophages. These cells are ‘primed’ by initial infection, allowing them to provide enhanced response to subsequent infection by the same or unrelated agent. This phenomenon of innate i
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50

Subiza, Jose Luis, Oscar Palomares, Isabella Quinti, and Silvia Sánchez-Ramón. "Editorial: Trained Immunity-Based Vaccines." Frontiers in Immunology 12 (June 24, 2021). http://dx.doi.org/10.3389/fimmu.2021.716296.

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