Publications
Here you can find the key publications from the members of the INTRIM consortium on the topic of trained immunity. Let us know if we missed any.
2025 to present
2025 to Present
Madsen, A. M. R., Schaltz-Buchholzer, F., Trebbien, R., Roring, R., Bang, N., Nielsen, C., Bliddal, M., Norberg, L. A., Netea, M. G., Barington, T., Aaby, P., Möller, S., & Benn, C. S. (2026). Evaluating the non-specific effects of BCG vaccination on the immune system and serological response to influenza vaccination in the elderly: A randomised controlled trial. Vaccine, 76, 128305. Advance online publication. https://doi.org/10.1016/j.vaccine.2026.128305
Koeken, V. A. C. M., Nissen, T. N., Birk, N. M., Boahen, C. K., van Crevel, R., Kumar, V., Li, Y., Aaby, P., Benn, C. S., & Netea, M. G. (2026). The effect of BCG vaccination on systemic inflammation in neonates. Vaccine, 75, 128241. https://doi.org/10.1016/j.vaccine.2026.128241
Merbecks, A. J., Mennicken, C., de Graaf, D. M., Shkarina, K., Wagner, T., & Latz, E. (2026). Western lifestyle linked to maladaptive trained immunity. eLife, 15, e105835. https://doi.org/10.7554/eLife.105835
Priem, B., Willemsen, L., Anbergen, T., ….. Joosten L.A.B., Fayad Z.A., Netea-Maier R.T., Netea M.G., de Winther M.P.J., Beldman T.J., Griffioen A.W., Mulder W.J.M. (2026). Systemically inducing trained immunity overcomes solid tumors’ immunosuppressive microenvironment. Science advances, 12(1), eadu0292. https://doi.org/10.1126/sciadv.adu0292
Riksen, N. P., Netea, M. G., Ait-Oufella, H., Chavakis, T., & Hajishengallis, G. (2025). Trained immunity in cardiovascular disease. European heart journal, ehaf982. Advance online publication. https://doi.org/10.1093/eurheartj/ehaf982
Qi, C., Liu, Z., Kilic, G., Sarlea, A. S., Debisarun, P. A., Liu, X., Mekonnen, Y. A., Li, W., Grasshoff, M., Alaswad, A., Petkoglou, A., Koeken, V. A. C. M., Moorlag, S. J. C. F. M., de Bree, L. C. J., Mourits, V. P., Joosten, L. A. B., Li, Y., Netea, M. G., & Xu, C. J. (2025). Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination. Genome biology, 26(1), 180. https://doi.org/10.1186/s13059-025-03611-9
Ziogas, A., Novakovic, B., Ventriglia, L., Galang, N., Tran, K. A., Li, W., Matzaraki, V., van Unen, N., Schlüter, T., Ferreira, A. V., Moorlag, S. J. C. F. M., Koeken, V. A. C. M., Moyo, M., Li, X., Baltissen, M. P. A., Martens, J. H. A., Li, Y., Divangahi, M., Joosten, L. A. B., Mhlanga, M. M., … Netea, M. G. (2025). Long-term histone lactylation connects metabolic and epigenetic rewiring in innate immune memory. Cell, 188(11), 2992–3012.e16. https://doi.org/10.1016/j.cell.2025.03.048
2020-2024
2023-2024
Yanginlar, C., Rother, N., Post, T. G. J. M., Jacobs, M., Jonkman, I., Brouns, M., Rinzema, S., Martens, J. H. A., Vermeulen, M., Joosten, L. A. B., Netea, M. G., Hilbrands, L. B., Choudhry, Z. A., van der Vlag, J., & Duivenvoorden, R. (2024). Trained innate immunity in response to nuclear antigens in systemic lupus erythematosus. Journal of autoimmunity, 149, 103335. https://doi.org/10.1016/j.jaut.2024.103335
Berendsen, M. L. T., Bles, P., de Bree, L. C. J., Jensen, K. J., Jensen, C. C., Wejse, C., Mendes, D. V., Netea, M. G., & Benn, C. S. (2024). Bacillus Calmette-Guérin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau. Vaccine, 42(26), 126439. https://doi.org/10.1016/j.vaccine.2024.126439
Lercher, A., Cheong, J. G., Bale, M. J., Jiang, C., Hoffmann, H. H., Ashbrook, A. W., Lewy, T., Yin, Y. S., Quirk, C., DeGrace, E. J., Chiriboga, L., Rosenberg, B. R., Josefowicz, S. Z., & Rice, C. M. (2024). Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease. Immunity, 57(11), 2530–2546.e13. https://doi.org/10.1016/j.immuni.2024.08.018
Jacobs, M. M. E., Maas, R. J. F., Jonkman, I., Negishi, Y., Tielemans Zamora, W., Yanginlar, C., van Heck, J., Matzaraki, V., Martens, J. H. A., Baltissen, M., Vermeulen, M., Morla-Folch, J., Ranzenigo, A., Wang, W., Umali, M., Ochando, J., van der Vlag, J., Hilbrands, L. B., Joosten, L. A. B., Netea, M. G., … Duivenvoorden, R. (2024). Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling. Cell reports, 43(9), 114664. https://doi.org/10.1016/j.celrep.2024.114664
Sun, S. J., Aguirre-Gamboa, R., de Bree, L. C. J., Sanz, J., Dumaine, A., van der Velden, W. J. F. M., Joosten, L. A. B., Khader, S., Divangahi, M., Netea, M. G., & Barreiro, L. B. (2024). BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses. Immunity, 57(9), 2095–2107.e8. https://doi.org/10.1016/j.immuni.2024.07.021
Tran, K. A., Pernet, E., Sadeghi, M., Downey, J., Chronopoulos, J., Lapshina, E., Tsai, O., Kaufmann, E., Ding, J., & Divangahi, M. (2024). BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity. Nature immunology, 25(3), 418–431. https://doi.org/10.1038/s41590-023-01739-z
Moorlag, S. J. C. F. M., Folkman, L., Ter Horst, R., Krausgruber, T., Barreca, D., Schuster, L. C., Fife, V., Matzaraki, V., Li, W., Reichl, S., Mourits, V. P., Koeken, V. A. C. M., de Bree, L. C. J., Dijkstra, H., Lemmers, H., van Cranenbroek, B., van Rijssen, E., Koenen, H. J. P. M., Joosten, I., Xu, C. J., … Bock, C. (2024). Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity. Immunity, 57(1), 171–187.e14. https://doi.org/10.1016/j.immuni.2023.12.005
Fok, E. T., Moorlag, S. J. C. F. M., Negishi, Y., Groh, L. A., Dos Santos, J. C., Gräwe, C., Monge, V. V., Craenmehr, D. D. D., van Roosmalen, M., da Cunha Jolvino, D. P., Migliorini, L. B., Neto, A. S., Severino, P., Vermeulen, M., Joosten, L. A. B., Netea, M. G., Fanucchi, S., & Mhlanga, M. M. (2024). A chromatin-regulated biphasic circuit coordinates IL-1β-mediated inflammation. Nature genetics, 56(1), 85–99. https://doi.org/10.1038/s41588-023-01598-2
van Puffelen, J. H., Novakovic, B., van Emst, L., Kooper, D., Zuiverloon, T. C. M., Oldenhof, U. T. H., Witjes, J. A., Galesloot, T. E., Vrieling, A., Aben, K. K. H., Kiemeney, L. A. L. M., Oosterwijk, E., Netea, M. G., Boormans, J. L., van der Heijden, A. G., Joosten, L. A. B., & Vermeulen, S. H. (2023). Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections. Journal for immunotherapy of cancer, 11(1), e005518. https://doi.org/10.1136/jitc-2022-005518
Li, W., Moorlag, S. J. C. F. M., Koeken, V. A. C. M., Röring, R. J., de Bree, L. C. J., Mourits, V. P., Gupta, M. K., Zhang, B., Fu, J., Zhang, Z., Grondman, I., van Meijgaarden, K. E., Zhou, L., Alaswad, A., Joosten, L. A. B., van Crevel, R., Xu, C. J., Netea, M. G., & Li, Y. (2023). A single-cell view on host immune transcriptional response to in vivo BCG-induced trained immunity. Cell reports, 42(5), 112487. https://doi.org/10.1016/j.celrep.2023.112487
Schrijver, D. P., Röring, R. J., Deckers, J., de Dreu, A., Toner, Y. C., Prevot, G., Priem, B., Munitz, J., Nugraha, E. G., van Elsas, Y., Azzun, A., Anbergen, T., Groh, L. A., Becker, A. M. D., Pérez-Medina, C., Oosterwijk, R. S., Novakovic, B., Moorlag, S. J. C. F. M., Jansen, A., Pickkers, P., … Mulder, W. J. M. (2023). Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells. Nature biomedical engineering, 7(9), 1097–1112. https://doi.org/10.1038/s41551-023-01050-0
2020-2022
Bannister, S., Kim, B., Domínguez-Andrés, J., Kilic, G., Ansell, B. R. E., Neeland, M. R., Moorlag, S. J. C. F. M., Matzaraki, V., Vlahos, A., Shepherd, R., Germano, S., Bahlo, M., Messina, N. L., Saffery, R., Netea, M. G., Curtis, N., & Novakovic, B. (2022). Neonatal BCG vaccination is associated with a long-term DNA methylation signature in circulating monocytes. Science advances, 8(31), eabn4002. https://doi.org/10.1126/sciadv.abn4002
Kaufmann, E., Khan, N., Tran, K. A., Ulndreaj, A., Pernet, E., Fontes, G., Lupien, A., Desmeules, P., McIntosh, F., Abow, A., Moorlag, S. J. C. F. M., Debisarun, P., Mossman, K., Banerjee, A., Karo-Atar, D., Sadeghi, M., Mubareka, S., Vinh, D. C., King, I. L., Robbins, C. S., … Divangahi, M. (2022). BCG vaccination provides protection against IAV but not SARS-CoV-2. Cell reports, 38(10), 110502. https://doi.org/10.1016/j.celrep.2022.110502
Kong, L., Moorlag, S. J. C. F. M., Lefkovith, A., Li, B., Matzaraki, V., van Emst, L., Kang, H. A., Latorre, I., Jaeger, M., Joosten, L. A. B., Netea, M. G., & Xavier, R. J. (2021). Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes. Cell reports, 37(7), 110028. https://doi.org/10.1016/j.celrep.2021.110028
Divangahi, M., Aaby, P., Khader, S. A., Barreiro, L. B., Bekkering, S., Chavakis, T., van Crevel, R., Curtis, N., DiNardo, A. R., Dominguez-Andres, J., Duivenvoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K. L., Khan, N., Joosten, L. A. B., Kaufmann, E., Latz, E., … Netea, M. G. (2021). Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nature immunology, 22(1), 2–6. https://doi.org/10.1038/s41590-020-00845-6
de Bree, L. C. J., Mourits, V. P., Koeken, V. A., Moorlag, S. J., Janssen, R., Folkman, L., Barreca, D., Krausgruber, T., Fife-Gernedl, V., Novakovic, B., Arts, R. J., Dijkstra, H., Lemmers, H., Bock, C., Joosten, L. A., van Crevel, R., Benn, C. S., & Netea, M. G. (2020). Circadian rhythm influences induction of trained immunity by BCG vaccination. The Journal of clinical investigation, 130(10), 5603–5617. https://doi.org/10.1172/JCI133934
Koeken, V. A., de Bree, L. C. J., Mourits, V. P., Moorlag, S. J., Walk, J., Cirovic, B., Arts, R. J., Jaeger, M., Dijkstra, H., Lemmers, H., Joosten, L. A., Benn, C. S., van Crevel, R., & Netea, M. G. (2020). BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner. The Journal of clinical investigation, 130(10), 5591–5602. https://doi.org/10.1172/JCI133935
Kalafati, L., Kourtzelis, I., Schulte-Schrepping, J., Li, X., Hatzioannou, A., Grinenko, T., Hagag, E., Sinha, A., Has, C., Dietz, S., de Jesus Domingues, A. M., Nati, M., Sormendi, S., Neuwirth, A., Chatzigeorgiou, A., Ziogas, A., Lesche, M., Dahl, A., Henry, I., Subramanian, P., … Chavakis, T. (2020). Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity. Cell, 183(3), 771–785.e12. https://doi.org/10.1016/j.cell.2020.09.058
Cirovic, B., de Bree, L. C. J., Groh, L., Blok, B. A., Chan, J., van der Velden, W. J. F. M., Bremmers, M. E. J., van Crevel, R., Händler, K., Picelli, S., Schulte-Schrepping, J., Klee, K., Oosting, M., Koeken, V. A. C. M., van Ingen, J., Li, Y., Benn, C. S., Schultze, J. L., Joosten, L. A. B., Curtis, N., … Schlitzer, A. (2020). BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment. Cell host & microbe, 28(2), 322–334.e5. https://doi.org/10.1016/j.chom.2020.05.014
2015-2019
2017-2019
Khader, S. A., Divangahi, M., Hanekom, W., Hill, P. C., Maeurer, M., Makar, K. W., Mayer-Barber, K. D., Mhlanga, M. M., Nemes, E., Schlesinger, L. S., van Crevel, R., Vankayalapati, R., Xavier, R. J., Netea, M. G., & Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery Innate Immunity Working Group18 (2019). Targeting innate immunity for tuberculosis vaccination. The Journal of clinical investigation, 129(9), 3482–3491. https://doi.org/10.1172/JCI128877
Walk, J., de Bree, L. C. J., Graumans, W., Stoter, R., van Gemert, G. J., van de Vegte-Bolmer, M., Teelen, K., Hermsen, C. C., Arts, R. J. W., Behet, M. C., Keramati, F., Moorlag, S. J. C. F. M., Yang, A. S. P., van Crevel, R., Aaby, P., de Mast, Q., van der Ven, A. J. A. M., Stabell Benn, C., Netea, M. G., & Sauerwein, R. W. (2019). Outcomes of controlled human malaria infection after BCG vaccination. Nature communications, 10(1), 874. https://doi.org/10.1038/s41467-019-08659-3
Domínguez-Andrés, J., Novakovic, B., Li, Y., Scicluna, B. P., Gresnigt, M. S., Arts, R. J. W., Oosting, M., Moorlag, S. J. C. F. M., Groh, L. A., Zwaag, J., Koch, R. M., Ter Horst, R., Joosten, L. A. B., Wijmenga, C., Michelucci, A., van der Poll, T., Kox, M., Pickkers, P., Kumar, V., Stunnenberg, H., … Netea, M. G. (2019). The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell metabolism, 29(1), 211–220.e5. https://doi.org/10.1016/j.cmet.2018.09.003
Freyne, B., Donath, S., Germano, S., Gardiner, K., Casalaz, D., Robins-Browne, R. M., Amenyogbe, N., Messina, N. L., Netea, M. G., Flanagan, K. L., Kollmann, T., & Curtis, N. (2018). Neonatal BCG Vaccination Influences Cytokine Responses to Toll-like Receptor Ligands and Heterologous Antigens. The Journal of infectious diseases, 217(11), 1798–1808. https://doi.org/10.1093/infdis/jiy069
Arts, R. J. W., Moorlag, S. J. C. F. M., Novakovic, B., Li, Y., Wang, S. Y., Oosting, M., Kumar, V., Xavier, R. J., Wijmenga, C., Joosten, L. A. B., Reusken, C. B. E. M., Benn, C. S., Aaby, P., Koopmans, M. P., Stunnenberg, H. G., van Crevel, R., & Netea, M. G. (2018). BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell host & microbe, 23(1), 89–100.e5. https://doi.org/10.1016/j.chom.2017.12.010
Bekkering, S., Arts, R. J. W., Novakovic, B., Kourtzelis, I., van der Heijden, C. D. C. C., Li, Y., Popa, C. D., Ter Horst, R., van Tuijl, J., Netea-Maier, R. T., van de Veerdonk, F. L., Chavakis, T., Joosten, L. A. B., van der Meer, J. W. M., Stunnenberg, H., Riksen, N. P., & Netea, M. G. (2018). Metabolic Induction of Trained Immunity through the Mevalonate Pathway. Cell, 172(1-2), 135–146.e9. https://doi.org/10.1016/j.cell.2017.11.025
Mitroulis, I., Ruppova, K., Wang, B., Chen, L. S., Grzybek, M., Grinenko, T., Eugster, A., Troullinaki, M., Palladini, A., Kourtzelis, I., Chatzigeorgiou, A., Schlitzer, A., Beyer, M., Joosten, L. A. B., Isermann, B., Lesche, M., Petzold, A., Simons, K., Henry, I., Dahl, A., … Chavakis, T. (2018). Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell, 172(1-2), 147–161.e12. https://doi.org/10.1016/j.cell.2017.11.034
Christ, A., Günther, P., Lauterbach, M. A. R., Duewell, P., Biswas, D., Pelka, K., Scholz, C. J., Oosting, M., Haendler, K., Baßler, K., Klee, K., Schulte-Schrepping, J., Ulas, T., Moorlag, S. J. C. F. M., Kumar, V., Park, M. H., Joosten, L. A. B., Groh, L. A., Riksen, N. P., Espevik, T., … Latz, E. (2018). Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell, 172(1-2), 162–175.e14. https://doi.org/10.1016/j.cell.2017.12.013
Kaufmann, E., Sanz, J., Dunn, J. L., Khan, N., Mendonça, L. E., Pacis, A., Tzelepis, F., Pernet, E., Dumaine, A., Grenier, J. C., Mailhot-Léonard, F., Ahmed, E., Belle, J., Besla, R., Mazer, B., King, I. L., Nijnik, A., Robbins, C. S., Barreiro, L. B., & Divangahi, M. (2018). BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis. Cell, 172(1-2), 176–190.e19. https://doi.org/10.1016/j.cell.2017.12.031
2015-2016
Arts, R. J., Novakovic, B., Ter Horst, R., Carvalho, A., Bekkering, S., Lachmandas, E., Rodrigues, F., Silvestre, R., Cheng, S. C., Wang, S. Y., Habibi, E., Gonçalves, L. G., Mesquita, I., Cunha, C., van Laarhoven, A., van de Veerdonk, F. L., Williams, D. L., van der Meer, J. W., Logie, C., O’Neill, L. A., … Netea, M. G. (2016). Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. Cell metabolism, 24(6), 807–819. https://doi.org/10.1016/j.cmet.2016.10.008
Arts, R. J. W., Carvalho, A., La Rocca, C., Palma, C., Rodrigues, F., Silvestre, R., Kleinnijenhuis, J., Lachmandas, E., Gonçalves, L. G., Belinha, A., Cunha, C., Oosting, M., Joosten, L. A. B., Matarese, G., van Crevel, R., & Netea, M. G. (2016). Immunometabolic Pathways in BCG-Induced Trained Immunity. Cell reports, 17(10), 2562–2571. https://doi.org/10.1016/j.celrep.2016.11.011
Novakovic, B., Habibi, E., Wang, S. Y., Arts, R. J. W., Davar, R., Megchelenbrink, W., Kim, B., Kuznetsova, T., Kox, M., Zwaag, J., Matarese, F., van Heeringen, S. J., Janssen-Megens, E. M., Sharifi, N., Wang, C., Keramati, F., Schoonenberg, V., Flicek, P., Clarke, L., Pickkers, P., … Stunnenberg, H. G. (2016). β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance. Cell, 167(5), 1354–1368.e14. https://doi.org/10.1016/j.cell.2016.09.034
Netea, M. G., Joosten, L. A., Latz, E., Mills, K. H., Natoli, G., Stunnenberg, H. G., O’Neill, L. A., & Xavier, R. J. (2016). Trained immunity: A program of innate immune memory in health and disease. Science, 352(6284), aaf1098. https://doi.org/10.1126/science.aaf1098
2014 and older
2014 and older
Kleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L. A., Jacobs, C., Xavier, R. J., van der Meer, J. W., van Crevel, R., & Netea, M. G. (2014). BCG-induced trained immunity in NK cells: Role for non-specific protection to infection. Clinical immunology, 155(2), 213–219. https://doi.org/10.1016/j.clim.2014.10.005
Buffen, K., Oosting, M., Quintin, J., Ng, A., Kleinnijenhuis, J., Kumar, V., van de Vosse, E., Wijmenga, C., van Crevel, R., Oosterwijk, E., Grotenhuis, A. J., Vermeulen, S. H., Kiemeney, L. A., van de Veerdonk, F. L., Chamilos, G., Xavier, R. J., van der Meer, J. W., Netea, M. G., & Joosten, L. A. (2014). Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. PLoS pathogens, 10(10), e1004485. https://doi.org/10.1371/journal.ppat.1004485
Saeed, S., Quintin, J., Kerstens, H. H., Rao, N. A., Aghajanirefah, A., Matarese, F., Cheng, S. C., Ratter, J., Berentsen, K., van der Ent, M. A., Sharifi, N., Janssen-Megens, E. M., Ter Huurne, M., Mandoli, A., van Schaik, T., Ng, A., Burden, F., Downes, K., Frontini, M., Kumar, V., … Stunnenberg, H. G. (2014). Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science, 345(6204), 1251086. https://doi.org/10.1126/science.1251086
Cheng, S. C., Quintin, J., Cramer, R. A., Shepardson, K. M., Saeed, S., Kumar, V., Giamarellos-Bourboulis, E. J., Martens, J. H., Rao, N. A., Aghajanirefah, A., Manjeri, G. R., Li, Y., Ifrim, D. C., Arts, R. J., van der Veer, B. M., Deen, P. M., Logie, C., O’Neill, L. A., Willems, P., van de Veerdonk, F. L., … Netea, M. G. (2014). mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science, 345(6204), 1250684. https://doi.org/10.1126/science.1250684