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Cross-kingdom mechanisms of trained immunity in plant systemic acquired resistance

Nature Plants (2025)Cite this article

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Abstract

Plants face constant microbial threats and have evolved highly effective immune systems characterized by inducible defence mechanisms. On recognizing microbial patterns and/or effectors, plants activate localized pattern-triggered immunity and/or effector-triggered immunity, which culminate in systemic acquired resistance—a broad-spectrum immune response that enhances protection throughout the plant. Systemic acquired resistance shares striking similarities with mammalian trained immunity, particularly in defence priming, which equips organisms with an enhanced capacity to respond to subsequent infections. This Review explores the cross-kingdom similarities between systemic acquired resistance and trained immunity, emphasizing their potential to transform agricultural practices and medical therapies. These insights present innovative opportunities for developing new plant-protection strategies, producing disease-resistant crops and optimizing vaccine approaches, while also highlighting critical knowledge gaps to inspire future research.

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Fig. 1: SAR in the upper leaves of tobacco plants.
Fig. 2: The three-phase Z model of SAR.
Fig. 3: States of cells and known common molecular mechanisms during the activation of SAR and trained immunity in a chimeric plant–mammalian innate immune cell.

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References

  1. Ross, A. F. Systemic acquired resistance induced by localized virus infections in plants. Virology 14, 340–358 (1961). This paper represents a seminal milestone in plant immunology, establishing the concept of systemic acquired resistance in plants.

    Article  CAS  PubMed  Google Scholar 

  2. Malamy, J., Carr, J. P., Klessig, D. F. & Raskin, I. Salicylic acid: a likely endogenous signal in the resistance response of tobacco to viral infection. Science 250, 1002–1004 (1990).

    Article  CAS  PubMed  Google Scholar 

  3. Dean, R. A. & Kuć, J. Induced systemic protection in plants. Trends Biotechnol. 3, 125–129 (1985).

    Article  Google Scholar 

  4. Ryals, J. A. et al. Systemic acquired resistance. Plant Cell 8, 1809–1819 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fu, Z. Q. & Dong, X. Systemic acquired resistance: turning local infection into global defence. Annu. Rev. Plant Biol. 64, 839–863 (2013).

    Article  CAS  PubMed  Google Scholar 

  6. Mishina, T. E. & Zeier, J. The Arabidopsis flavin-dependent monooxygenase FMO1 is an essential component of biologically induced systemic acquired resistance. Plant Physiol. 141, 1666–1675 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hartmann, M. et al. Flavin monooxygenase-generated N-hydroxypipecolic acid is a critical element of plant systemic immunity. Cell 173, 456–469 (2018).

    Article  CAS  PubMed  Google Scholar 

  8. Návarová, H., Bernsdorff, F., Döring, A.-C. & Zeier, J. Pipecolic acid, an endogenous mediator of defence amplification and priming, is a critical regulator of inducible plant immunity. Plant Cell 24, 5123–5141 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Luna, E. et al. Next-generation systemic acquired resistance. Plant Physiol. 158, 844–853 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Jones, J. D. G. & Dangl, J. L. The plant immune system. Nature 444, 323–329 (2006). This landmark paper elucidates the complex network of local defence mechanisms used by plants against pathogens, serving as a foundational reference for plant immunologists.

    Article  CAS  PubMed  Google Scholar 

  11. Jones, J. D., Staskawicz, B. J. & Dangl, J. L. The plant immune system: from discovery to deployment. Cell 187, 2095–2116 (2024). This article summarizes the current knowledge of extracellular and intracellular receptors that convert recognition of extracellular microbial patterns or intracellular pathogen-delivered virulence effectors into downstream signalling and local defence activation.

    Article  CAS  PubMed  Google Scholar 

  12. Padgett, H. S., Watanabe, Y. & Beachy, R. N. Identification of the TMV replicase sequence that activates the N gene-mediated hypersensitive response. Mol. Plant Microbe Interact. 10, 709–715 (1997).

    Article  CAS  Google Scholar 

  13. Gruner, K. et al. Reprograming of plants during systemic acquired resistance. Front. Plant Sci. 4, 252 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Powers, J. et al. Next-generation mapping of the salicylic acid signalling hub and transcriptional cascade. Mol. Plant 17, 1558–1572 (2024). This study uncovers the NPR1 proxiome and its role in SA-induced plant immunity, revealing how NPR1 condensates orchestrate transcriptional cascades through chromatin remodelling and transcription factor recruitment, providing a blueprint for mapping signalling hubs in plant immunity.

    Article  CAS  PubMed  Google Scholar 

  15. Baum, S. et al. Isolation of open chromatin identifies regulators of systemic acquired resistance. Plant Physiol. 181, 817–833 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sistenich, A. J. et al. Marker and readout genes for defence priming in Pseudomonas cannabina pv. alisalensis interaction aid understanding systemic immunity in Arabidopsis. Sci. Rep. 14, 3489 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schwachtje, J., Fischer, A., Erban, A. & Kopka, J. Primed primary metabolism in systemic leaves: a functional systems analysis. Sci. Rep. 8, 216 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhang, H., Liu, Y., Zhang, X., Ji, W. & Kang, Z. A necessary considering factor for breeding: growth–defence trade-off in plants. Stress Biol. 3, 6 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Huot, B., Yao, J., Montgomery, B. L. & He, S. Y. Growth–defence trade-offs in plants: a balancing act to optimize fitness. Mol. Plant 7, 1267–1287 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Conrath, U. et al. Priming: getting ready for battle. Mol. Plant Microbe Interact. 19, 1062–1071 (2006).

    Article  CAS  PubMed  Google Scholar 

  21. Conrath, U. et al. Priming for enhanced defence. Annu. Rev. Phytopathol. 53, 97–119 (2015).

    Article  CAS  PubMed  Google Scholar 

  22. Spoel, S. H. & Dong, X. How do plants achieve immunity? Defence without specialized immune cells. Nat. Rev. Immunol. 12, 89–100 (2012).

    Article  CAS  PubMed  Google Scholar 

  23. Ausubel, F. M. Are innate immune signalling pathways in plants and animals conserved? Nat. Immunol. 6, 973–979 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Roberts, D. A. Acquired resistance to tobacco mosaic virus transmitted to the progeny of hypersensitive tobacco. Virology 124, 161–163 (1983).

    Article  CAS  PubMed  Google Scholar 

  25. Slaughter, A. et al. Descendants of primed Arabidopsis plants exhibit resistance to biotic stress. Plant Physiol. 158, 835–843 (2012).

    Article  CAS  PubMed  Google Scholar 

  26. Lamarck, J.-B. P. A. Philosophie Zoologique Vol. 1, ou Exposition des Considérations Relatives à l’Histoire Naturelle des Animaux (Dentu, 1809). In this book, Lamarck proposed that species could acquire new traits through environmental influences.

  27. Pradeu, T. et al. The conceptual foundations of innate immunity: taking stock 30 years later. Immunity 57, 613–631 (2024).

    Article  CAS  PubMed  Google Scholar 

  28. Netea, M. G. et al. Trained immunity: a memory for innate host defence. Cell Host Microbe 9, 355–361 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Kurtz, J. & Franz, K. Evidence for memory in invertebrate immunity. Nature 425, 37–38 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Moret, Y. & Siva-Jothy, T. Adaptive innate immunity? Responsive-mode prophylaxis in the mealworm beetle, Tenebrio molitor. Proc. R. Soc. B 270, 2475–2480 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Netea, M. G. et al. Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098 (2016). This is a pivotal contribution that elucidates the concept of trained immunity, revolutionizing our understanding of the innate immune system’s ability to mount enhanced responses to subsequent infections, with profound implications for human health and disease.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Netea, M. G. et al. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 20, 375–388 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sun, J. C., Beilke, J. N. & Lanier, L. L. Adaptive immune features of natural killer cells. Nature 457, 557–561 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Stewart, W. E., Gosser, L. B. & Lockart, R. Z. Priming: a non-anti-viral function of interferon. J. Virol. 7, 792–801 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Abreu, S. L., Bancroft, F. C. & Stewart, W. E. Interferon priming: effects on interferon messenger RNA. J. Biol. Chem. 254, 4114–4118 (1979).

    Article  CAS  PubMed  Google Scholar 

  36. Gifford, G. E. & Lohmann-Matthes, M.-L. Gamma interferon priming of mouse and human macrophages for induction of tumour necrosis factor production by bacterial lipopolysaccharide. J. Natl Cancer Inst. 78, 121–124 (1987).

    Article  CAS  PubMed  Google Scholar 

  37. Koerner, T. J., Adams, D. O. & Hamilton, T. A. Regulation of tumour necrosis factor (TNF) expression: interferon-ɣ enhances the accumulation of mRNA for TNF induced by polysaccharide in murine peritoneal macrophages. Cell. Immunol. 109, 437–443 (1987).

    Article  CAS  PubMed  Google Scholar 

  38. Hayes, M. P., Enterline, J. C., Gerrard, T. L. & Zoon, K. C. Regulation of interferon production by human monocytes: requirements for priming for lipopolysaccharide-induced production. J. Leukoc. Biol. 50, 176–181 (1991).

    Article  CAS  PubMed  Google Scholar 

  39. Hayes, M. P., Freeman, S. L. & Donnelly, R. P. IFN-ɣ priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and mRNA stability. Cytokine 7, 427–435 (1995).

    Article  CAS  PubMed  Google Scholar 

  40. Hayes, M. P., Wang, J. & Norcross, M. A. Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-ɣ of lipopolysaccharide-inducible p35 and p40 genes. Blood 86, 646–650 (1995).

    Article  CAS  PubMed  Google Scholar 

  41. Hayes, M. P. & Zoon, K. C. Priming of human monocytes for enhanced lipopolysaccharide responses: expression of alpha interferon, interferon regulatory factors, and tumour necrosis factor. Infect. Immun. 61, 3222–3227 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hoffmann, H.-H., Schneider, W. M. & Rice, C. M. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol. 36, 124–138 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Quintin, J. et al. Candida albicans infection affords protection against reinfection via functional reprograming of monocytes. Cell Host Microbe 12, 223–232 (2012).

    Article  CAS  PubMed  Google Scholar 

  44. Vuscan, P. et al. Potent induction of trained immunity by Saccharomyces cerevisiae β-glucans. Front. Immunol. 15, 1323333 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang, G. et al. β-Glucan induces trained immunity to promote anti-viral activity by activating TBK1. Viruses 15, 1204 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Van Aubel, G., Cambier, P., Dieu, M. & Van Cutsem, P. Plant immunity induced by COS-OGA elicitor is a cumulative process that involves salicylic acid. Plant Sci. 247, 60–70 (2016).

    Article  PubMed  Google Scholar 

  47. Grebenciucova, E. & VanHaerents, S. Interleukin 6: at the interface of human health and disease. Front. Immunol. 14, 1255533 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ciarlo, E. et al. Trained immunity confers broad-spectrum protection against bacterial infections. J. Infect. Dis. 222, 1869–1881 (2020).

    Article  CAS  PubMed  Google Scholar 

  49. Katzmarski, N. et al. Transmission of trained immunity and heterologous resistance to infection across generations. Nat. Immunol. 22, 1382–1390 (2021).

    Article  CAS  PubMed  Google Scholar 

  50. Métraux, J. P. et al. Increase in salicylic acid at the onset of systemic acquired resistance in cucumber. Science 250, 1004–1006 (1990).

    Article  PubMed  Google Scholar 

  51. Shulaev, V., Leon, J. & Raskin, I. Is salicylic acid a translocated signal of systemic acquired resistance in tobacco? Plant Cell 7, 1691–1701 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Shulaev, V., Silverman, P. & Raskin, I. Airborne signalling by methyl salicylate in plant pathogen resistance. Nature 385, 718–721 (1997).

    Article  CAS  Google Scholar 

  53. Park, S.-W., Kaimoyo, E., Kumar, D., Mosher, S. & Klessig, D. F. Methyl salicylate is a critical mobile signal for plant systemic acquired resistance. Science 318, 113–116 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Truman, W., Bennett, M. H., Kubigsteltig, I., Turnbull, C. & Grant, M. Arabidopsis systemic immunity uses conserved defence signalling pathways and is mediated by jasmonates. Proc. Natl Acad. Sci. USA 104, 1075–1080 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jung, H. W., Tschaplinski, T. J., Wang, L., Glazebrook, J. & Greenberg, J. T. Priming in systemic plant immunity. Science 324, 89–91 (2009).

    Article  PubMed  Google Scholar 

  56. Chaturvedi, R. et al. An abietane diterpenoid is a potent activator of systemic acquired resistance. Plant J. 71, 161–172 (2012).

    Article  CAS  PubMed  Google Scholar 

  57. Li, Q. et al. N-hydroxypipecolic acid triggers systemic acquired resistance through extracellular NAD(P). Nat. Commun. 14, 6848 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Chen, Y.-C. et al. N-hydroxypipecolic acid is a mobile metabolite that induces systemic disease resistance in Arabidopsis. Proc. Natl Acad. Sci. USA 115, E4920–E4929 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Shine, M. B. et al. Phased small RNA–mediated systemic signalling in plants. Sci. Adv. 8, eabm8791 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Alvarez, M. E. et al. Reactive oxygen intermediates mediate a systemic signal network in the establishment of plant immunity. Cell 92, 773–784 (1998).

    Article  CAS  PubMed  Google Scholar 

  61. Cao, L. et al. H2O2 sulfenylates CHE, linking local infection to the establishment of systemic acquired resistance. Science 385, 1211–1217 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Maldonado, A. M., Doerner, P., Dixon, R. A., Lamb, C. J. & Cameron, R. K. A putative lipid transfer protein involved in systemic resistance signalling in Arabidopsis. Nature 419, 399–403 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. Chanda, B. et al. Glycerol-3-phosphate is a critical mobile inducer of systemic immunity in plants. Nat. Genet. 43, 421–427 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Riedlmeier, M. et al. Monoterpenes support systemic acquired resistance within and between plants. Plant Cell 29, 1440–1459 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wenig, M. et al. Systemic acquired resistance networks amplify airborne defence cues. Nat. Commun. 10, 3813 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Brambilla, A. et al. Immunity-associated volatile emissions of β-ionone and nonanal propagate defence responses in neighbouring barley plants. J. Exp. Bot. 73, 615–630 (2022).

    Article  CAS  PubMed  Google Scholar 

  67. Brambilla, A. et al. Pipecolic acid synthesis is required for systemic acquired resistance and plant-to-plant-induced immunity in barley. J. Exp. Bot. 19, 3033–3046 (2013).

    Google Scholar 

  68. Delaney, T. P. et al. A central role of salicylic acid in plant disease resistance. Science 266, 1247–1250 (1994).

    Article  CAS  PubMed  Google Scholar 

  69. Šestan, M. et al. An IFNγ-dependent immune–endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune response. Nat. Immunol. 25, 981–993 (2024).

    Article  PubMed  Google Scholar 

  70. Fanucchi, S., Dominguez-Andrea, J., Joosten, L. A. B., Netea, M. G. & Mhlanga, M. M. The intersection of epigenetics and metabolism in trained immunity. Immunity 54, 32–43 (2021).

    Article  CAS  PubMed  Google Scholar 

  71. Bhargavi, G. & Subbian, S. The causes and consequences of trained immunity in myeloid cells. Front. Immunol. 15, 1365127 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang, D., Weaver, N. D., Kesarwani, M. & Dong, X. Induction of protein secretory pathway is required for systemic acquired resistance. Science 308, 1036–1040 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Kohler, A., Schwindling, S. & Conrath, U. Benzothiadiazole-induced priming for potentiated responses to pathogen infection, wounding, and infiltration of water into leaves requires the NPR1/NIM1 gene in Arabidopsis. Plant Physiol. 128, 1046–1056 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zavaliev, R. & Dong, X. NPR1, a key immune regulator for plant survival under biotic and abiotic stresses. Mol. Cell 84, 131–141 (2024).

    Article  CAS  PubMed  Google Scholar 

  75. Chhillar, H., Nguyen, H. H., Yeh, P.-M., Jones, J. D. G. & Ding, P. Modular mechanisms of immune priming and growth inhibition mediated by plant effector-triggered immunity. Cell Rep. 44, 115394 (2025).

    Article  CAS  PubMed  Google Scholar 

  76. Wang et al. The truncated TNL receptor TN2-mediated immune responses require ADR1 function. Plant J. 108, 672–689 (2021).

    Article  CAS  PubMed  Google Scholar 

  77. Pick, T., Jaskiewicz, M., Peterhänsel, C. & Conrath, U. Heat shock factor HsfB1 primes gene transcription and systemic acquired resistance in Arabidopsis. Plant Physiol. 159, 52–55 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Pajerowska-Mukhatar, K. M. et al. The HSF-like transcription factor TBF1 is a major molecular switch for plant growth-to-defence transition. Curr. Biol. 22, 103–112 (2012).

    Article  Google Scholar 

  79. Van Anken, E. et al. Sequential waves of functionally related proteins are expressed when B cells prepare for antibody secretion. Immunity 18, 243–253 (2003).

    Article  PubMed  Google Scholar 

  80. Beckers, G. J. M. et al. Mitogen-activated protein kinases 3 and 6 are required for full priming of stress responses in Arabidopsis thaliana. Plant Cell 21, 944–953 (2009). This study identifies MAPK3 and MAPK6 as key latent signalling components accumulated during SAR, revealing a molecular basis for defence priming against biotic and abiotic stress.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Tateda, C. et al. Salicylic acid regulates Arabidopsis microbial pattern receptor kinase levels and signalling. Plant Cell 26, 4171–4187 (2014). This study elucidates the crucial role of salicylic acid in enhancing microbial pattern receptor levels in primed Arabidopsis plants, shedding light on an intricate mechanism of plant defence priming.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gómez-Gómez, L. & Boller, T. FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol. Cell 5, 1003–1011 (2000).

    Article  PubMed  Google Scholar 

  83. Chinchilla, D. et al. A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448, 497–500 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Boller, T. & Felix, G. A renaissance of elicitors: perception of microbe-associated molecular patterns and danger signals by pattern-recognition receptors. Annu. Rev. Plant Biol. 60, 379–406 (2009).

    Article  CAS  PubMed  Google Scholar 

  85. Mithoe, S. C. & Menke, F. L. H. Regulation of pattern recognition receptor signalling by phosphorylation and ubiquitination. Curr. Opin. Plant Biol. 45, 162–170 (2018).

    Article  CAS  PubMed  Google Scholar 

  86. Gong, B.-Q. et al. Cross-microbial protection via priming a conserved immune co-receptor through juxtamembrane phosphorylation in plants. Cell Host Microbe 26, 810–822 (2019).

    Article  CAS  PubMed  Google Scholar 

  87. Sirén, J., Pirhonen, J., Julkunen, I. & Matikainen, S. IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29. J. Immunol. 174, 1932–1937 (2005).

    Article  PubMed  Google Scholar 

  88. Schroder, K., Sweet, M. J. & Hume, D. A. Signal integration between IFN-γ and TLR signalling pathways in macrophages. Immunobiology 211, 511–524 (2006). This study reveals that natural killer cells exhibit adaptive immune features, challenging the traditional distinction between innate and adaptive immunity.

    Article  CAS  PubMed  Google Scholar 

  89. Badeaux, A. I. & Shi, Y. Emerging roles for chromatin as a signal integration and storage platform. Nat. Rev. Mol. Cell Biol. 14, 211–224 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Roudier, F. et al. Integrative epigenomic mapping defines four main chromatin states in Arabidopsis. EMBO J. 30, 1928–1938 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ng, M. K. & Cheung, P. A brief histone in time: understanding the combinatorial functions of histone PTMs in the nucleosome context. Biochem. Cell Biol. 94, 33–42 (2016).

    Article  CAS  PubMed  Google Scholar 

  93. Peña, P. V. et al. Molecular mechanism of histone H3K4me3 recognition by plant homeo-domain of ING2. Nature 442, 100–103 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Kanno, T. et al. Selective recognition of acetylated histones by bromo-domain proteins visualized in living cells. Mol. Cell 13, 33–43 (2004).

    Article  CAS  PubMed  Google Scholar 

  95. Eberharter, A. & Becker, P. B. Histone acetylation: a switch between repressive and permissive chromatin. Second in review series on chromatin dynamics. EMBO Rep. 3, 224–229 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. He, G., Elling, A. A. & Deng, X. W. The epigenome and plant development. Annu. Rev. Plant Biol. 62, 411–435 (2011).

    Article  CAS  PubMed  Google Scholar 

  97. Jaskiewicz, M., Conrath, U. & Peterhänsel, C. Chromatin modification acts as a memory for systemic acquired resistance in the plant stress response. EMBO Rep. 12, 50–55 (2011). This paper reports that chromatin modifications serve as a molecular memory for SAR, enabling plants to mount faster and stronger defence responses upon reinfection.

    Article  CAS  PubMed  Google Scholar 

  98. Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Zhu, D. et al. Distinct chromatin signatures in the Arabidopsis male gametophyte. Nat. Genet. 55, 706–720 (2013).

    Article  Google Scholar 

  100. Keating, S. T. et al. The Set7 lysine methyltransferase regulates plasticity in oxidative phosphorylation necessary for trained immunity induced by β-glucan. Cell Rep. 31, 107548 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Henikoff, S. Nucleosome destabilization in the epigenetic regulation of gene expression. Nat. Rev. Genet. 9, 15–26 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. Gaulton, K. J. et al. A map of open chromatin in human pancreatic islets. Nat. Genet. 42, 255–259 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Buenrosto, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).

    Article  Google Scholar 

  104. Kleinnijenhuis, J. et al. Bacille Calmette–Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc. Natl Acad. Sci. USA 109, 17537–17542 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kaufmann, E. et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190 (2018). This study reveals that BCG reprogrammes hematopoietic stem cells in the bone marrow, leading to sustained innate immune memory and enhanced macrophage-mediated protection against tuberculosis, offering new insights for vaccine development.

    Article  CAS  PubMed  Google Scholar 

  106. Pavet, V. et al. Arabidopsis displays centromeric DNA hypomethylation and cytological alterations of heterochromatin upon attack by Pseudomonas syringae. Mol. Plant Microbe Interact. 19, 577–587 (2006).

    Article  CAS  PubMed  Google Scholar 

  107. Ptashne, M. Faddish stuff: epigenetics and the inheritance of acquired characteristics. FASEB J. 27, 1–2 (2013).

    Article  CAS  PubMed  Google Scholar 

  108. Baird, L. M., Berndsen, C. E. & Monroe, J. D. Malate dehydrogenase in plants: evolution, structure, and a myriad of functions. Essays Biochem. 68, 221–233 (2014).

    Google Scholar 

  109. Pracharoenwattana, I. et al. Arabidopsis has a cytosolic fumarase required for the massive allocation of photosynthate into fumaric acid and for rapid plant growth on high nitrogen. Plant J. 62, 785–795 (2010).

    Article  CAS  PubMed  Google Scholar 

  110. Fernie, A. R., Carrari, F. & Sweetlove, L. J. Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr. Opin. Plant Biol. 7, 254–261 (2004).

    Article  CAS  PubMed  Google Scholar 

  111. Zamboni, N., Fendt, S.-M., Rühl, M. & Sauer, U. 13C-based metabolic flux analysis. Nat. Protoc. 4, 878–892 (2009).

    Article  CAS  PubMed  Google Scholar 

  112. Balmer, A., Pastor, V., Glauser, G. & Mauch-Mani, B. Tricarboxylates induce defence priming against bacteria in Arabidopsis thaliana. Front. Plant Sci. 9, 1221 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Zimmerli, L., Jakab, G., Métraux, J.-P. & Mauch-Mani, B. Potentiation of pathogen-specific defence mechanisms in Arabidopsis by β-aminobutyric acid. Proc. Natl Acad. Sci. USA 97, 12920–12925 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Jakab, G. et al. β-aminobutyric acid-induced resistance in plants. Eur. J. Plant Pathol. 107, 29–37 (2001).

    Article  CAS  Google Scholar 

  115. Arts, R. J. et al. Glutaminolysis and fumarate accumulation integrate immune-metabolic and epigenetic programs in trained immunity. Cell Metab. 24, 807–819 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Zhang, X. & Mou, Z. Extracellular pyridine nucleotides induce PR gene expression and disease resistance in Arabidopsis. Plant J. 57, 302–312 (2009).

    Article  CAS  PubMed  Google Scholar 

  117. Wang, C. et al. Extracellular pyridine nucleotides trigger plant systemic immunity through a lectin receptor kinase/BAK1 complex. Nat. Commun. 10, 4810 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Pétriacq, P. et al. NAD acts as an integral regulator of multiple defence layers. Plant Physiol. 172, 1465–1479 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Adriouch, S. et al. NAD+ released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo. J. Immunol. 179, 186–194 (2007).

    Article  CAS  PubMed  Google Scholar 

  120. Minhas, P. S. et al. Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation. Nat. Immunol. 20, 50–63 (2019).

    Article  CAS  PubMed  Google Scholar 

  121. Hong, S. et al. Differential regulation of P2X7 receptor activation by extracellular NAD and ecto-ARTs in murine macrophages and T cells. J. Immunol. 183, 578–592 (2009).

    Article  CAS  PubMed  Google Scholar 

  122. Lee, H. C. Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP) as messengers for calcium mobilization. J. Biol. Chem. 287, 31633–31640 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Cheng, S. C. et al. mTOR- and HIF-1a–mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345, 1250684 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Cameron, A. M. et al. Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species-mediated DNA damage. Nat. Immunol. 20, 420–432 (2019).

    Article  CAS  PubMed  Google Scholar 

  125. Imai, S.-i & Guarente, L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 24, 464–471 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Acevedo, O. A. et al. Molecular and cellular mechanisms modulating trained immunity by various cell types in response to pathogen encounter. Front. Immunol. 12, 745332 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhong, L. et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140, 280–293 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Heinrich, P. C., Behrmann, I., Müller-Newen, G., Schaper, F. & Graeve, L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J. 334, 297–324 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Reeh, H. et al. Response to IL-6 trans- and IL-6 classic signalling is determined by the ratio of the IL-6 receptor α to gp130 expression: fusing experimental insights and dynamic modelling. Cell Commun. Signal. 17, 46 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Hu, X. & Ivashkiv, L. B. Cross-regulation of signalling and immune responses by IFN-ɣ and STAT1. Immunity 31, 539–550 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Wu, F. et al. Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis. Nature 578, 577–581 (2020).

    Article  CAS  PubMed  Google Scholar 

  132. Ding, Y. et al. Opposite roles of salicylic acid receptors NPR1 and NPR3/NPR4 in transcriptional regulation of plant immunity. Cell 173, 1454–1467 (2018).

    Article  CAS  PubMed  Google Scholar 

  133. Spoel, S. H. & Dong, X. Salicylic acid in plant immunity and beyond. Plant Cell 36, 1451–1464 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Nair, A. et al. N-hydroxypipecolic acid-induced transcription requires the salicylic acid signalling pathway at basal SA levels. Plant Physiol. 187, 2803–2819 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Bauerle, P. A. & Baltimore, D. NF-kappa B: ten years after. Cell 87, 13–20 (1996).

    Article  Google Scholar 

  136. Vo, N. & Goodman, R. H. CREB-binding protein and p300 in transcriptional regulation. J. Biol. Chem. 276, 13505 (2001).

    Article  CAS  PubMed  Google Scholar 

  137. Ryals, J. et al. The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor IκB. Plant Cell 9, 425–439 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Kesanakurti, D., Sareddy, G. R., Babu, B. P. & Kirti, P. B. Mustard NPR1, a mammalian I-kappa-B homologue inhibits NF-kappa B activation in human GBM cell lines. Biochem. Biophys. Res. Commun. 390, 427–433 (2009).

    Article  CAS  PubMed  Google Scholar 

  139. Zhang, N. et al. Early-life exercise induces immune-metabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice. Nat. Commun. 15, 3103 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Liu, G. Y. & Sabatini, D. M. mTOR at the nexus of nutrition, growth, ageing and disease. Nat. Rev. Mol. Cell Biol. 21, 183–203 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Shi, L., Wu, Y. & Sheen, J. TOR signalling in plants: conservation and innovation. Development 145, dev160887 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  142. De Vleesschauwer, D. et al. Target of rapamycin signalling orchestrates growth–defence trade-offs in plants. N. Phytol. 217, 305–319 (2018).

    Article  Google Scholar 

  143. Aznar, N. R., Consolo, V. F., Salerno, G. L. & Martinez-Noel, G. M. A. TOR signalling downregulation increases resistance to the cereal killer Fusarium graminearum. Plant Signal. Behav. 13, e1414120 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Buffen, K. et al. Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. PLoS Pathog. 10, e1004485 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Fanucchi, S. et al. Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments. Nat. Genet. 51, 138–150 (2019).

    Article  CAS  PubMed  Google Scholar 

  146. Yu, Y. et al. Transcriptional landscape of pathogen-responsive lncRNAs in rice unveils the role of ALEX1 in jasmonate pathway and disease resistance. Plant Biotechnol. J. 18, 679–690 (2020).

    Article  CAS  PubMed  Google Scholar 

  147. Huang, J., Zhou, W., Zhang, X. & Li, Y. Roles of long non-coding RNAs in plant immunity. PLoS Pathog. 19, e1011340 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. López Sánchez, A., Stassen, J. H. M., Furci, L., Smith, L. M. & Ton, J. The role of DNA (de)methylation in immune responsiveness of Arabidopsis. Plant J. 88, 361–374 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Caldwell, B. A., Wu, Y., Wang, J. & Li, L. Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis. Cell Rep. 43, 113894 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Furci, L. et al. Identification and characterization of hypomethylated DNA loci controlling quantitative resistance in Arabidopsis. eLife 8, e40655 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Lee, S. C. et al. Chromatin remodelling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation. Cell 186, 4100–4116 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Lee, S. et al. DDM1-mediated gene body DNA methylation is associated with inducible activation of defence-related genes in Arabidopsis. Genome Biol. 24, 106 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Cambiagno, D. A., Torres, J. R. & Alvarez, M. E. Convergent epigenetic mechanisms avoid constitutive expression of immune receptor gene subsets. Front. Plant Sci. 12, 703667 (2012).

    Article  Google Scholar 

  154. Ando, S. et al. Priming for enhanced ARGONAUTE2 activation accompanies induced resistance to cucumber mosaic virus in Arabidopsis thaliana. Mol. Plant Pathol. 22, 19–30 (2021).

    Article  CAS  PubMed  Google Scholar 

  155. Wilkinson, S. W. et al. Long-lasting memory of jasmonic acid-dependent immunity requires DNA demethylation and ARGONAUTE1. Nat. Plants 9, 81–95 (2013).

    Article  Google Scholar 

  156. Ugarte, P. B. et al. Argonaute proteins confer immunity in all domains of life. Curr. Opin. Microbiol. 74, 102313 (2023).

    Article  Google Scholar 

  157. Farm to Fork Strategy: For a Fair, Healthy and Environmentally-Friendly Food System https://food.ec.europa.eu/horizontal-topics/farm-fork-strategy_en (European Commission, 2020).

  158. Martinez-Medina, A. et al. Recognizing plant defence priming. Trends Plant Sci. 21, 818–822 (2016).

    Article  CAS  PubMed  Google Scholar 

  159. Leadbeater, A. & Staub, T. in Induced Resistance for Plant Defence: A Sustainable Approach to Crop Protection 2nd edn (eds Walters, D. R. et al.) 300–315 (Wiley, 2014).

  160. Cao, H., Li, X. & Dong, X. Generation of broad-spectrum disease resistance by overexpression of an essential regulatory gene in systemic acquired resistance. Proc. Natl Acad. Sci. USA 95, 6531–6536 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Zhou, J. et al. Trained immunity contributes to the prevention of Mycobacterium tuberculosis infection, a novel role of autophagy. Emerg. Microbes Infect. 10, 578–588 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Sohrabi, Y. et al. Trained immunity as a novel approach against COVID‐19 with a focus on Bacillus Calmette–Guérin vaccine: mechanisms, challenges and perspectives. Clin. Transl. Immunol. 9, e1228 (2020).

    Article  CAS  Google Scholar 

  163. Wang, T. et al. Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs. Nat. Immunol. 24, 423–438 (2023).

    Article  CAS  PubMed  Google Scholar 

  164. Lérias, J. R. et al. Trained immunity for personalized cancer immunotherapy: current knowledge and future opportunities. Front. Microbiol. 10, 2924 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Usher, N. T. et al. Association of BCG vaccination in childhood with subsequent cancer diagnoses: a 60-year follow-up of a clinical trial. JAMA Netw. Open 2, e1912014 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Funes, S. C. et al. Trained immunity contribution to autoimmune and inflammatory disorders. Front. Immunol. 13, 868343 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Badii, M. et al. Trained immunity and inflammation in rheumatic diseases. Joint Bone Spine 89, 105364 (2022).

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Molecular Plant Physiology, RWTH Aachen University, Aachen, Germany

    Uwe Conrath

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Conrath, U. Cross-kingdom mechanisms of trained immunity in plant systemic acquired resistance. Nat. Plants (2025). https://doi.org/10.1038/s41477-025-02119-1

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