Transmission of trained immunity and heterologous resistance to infections across generations

doi:10.1038/s41590-021-01052-7

. 2021 Nov;22(11):1382-1390.

doi: 10.1038/s41590-021-01052-7. Epub 2021 Oct 18.

Transmission of trained immunity and heterologous resistance to infections across generations

Natalie Katzmarski^#¹, Jorge Domínguez-Andrés^#^{2

3}, Branko Cirovic^#¹, Georgios Renieris⁴, Eleonora Ciarlo⁵, Didier Le Roy⁵, Konstantin Lepikhov⁶, Kathrin Kattler⁶, Gilles Gasparoni⁶, Kristian Händler⁷, Heidi Theis⁷, Marc Beyer^{7

8}, Jos W M van der Meer⁹, Leo A B Joosten^{9

10}, Jörn Walter⁶, Joachim L Schultze^{8

11}, Thierry Roger^#⁵, Evangelos J Giamarellos-Bourboulis^#⁴, Andreas Schlitzer^#¹, Mihai G Netea^#^{9

10

12}

Affiliations

¹ Quantitative Systems Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
² Department of Internal Medicine and Radboud Center for Infectious diseases, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. Jorge.DominguezAndres@radboudumc.nl.
³ Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Jorge.DominguezAndres@radboudumc.nl.
⁴ Department 4th of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
⁵ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
⁶ Department of Genetics/Epigenetics, Saarland University, Saarbrücken, Germany.
⁷ Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
⁸ Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases, Bonn, Germany.
⁹ Department of Internal Medicine and Radboud Center for Infectious diseases, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
¹⁰ Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹ Department for Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
¹² Department for Immunology & Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

^# Contributed equally.

PMID: 34663978
DOI: 10.1038/s41590-021-01052-7

Transmission of trained immunity and heterologous resistance to infections across generations

Natalie Katzmarski et al. Nat Immunol. 2021 Nov.

. 2021 Nov;22(11):1382-1390.

doi: 10.1038/s41590-021-01052-7. Epub 2021 Oct 18.

Authors

Affiliations

¹ Quantitative Systems Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
² Department of Internal Medicine and Radboud Center for Infectious diseases, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. Jorge.DominguezAndres@radboudumc.nl.
³ Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Jorge.DominguezAndres@radboudumc.nl.
⁴ Department 4th of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
⁵ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
⁶ Department of Genetics/Epigenetics, Saarland University, Saarbrücken, Germany.
⁷ Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
⁸ Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases, Bonn, Germany.
⁹ Department of Internal Medicine and Radboud Center for Infectious diseases, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
¹⁰ Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹ Department for Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
¹² Department for Immunology & Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

^# Contributed equally.

PMID: 34663978
DOI: 10.1038/s41590-021-01052-7

Erratum in

Author Correction: Transmission of trained immunity and heterologous resistance to infections across generations.
Katzmarski N, Domínguez-Andrés J, Cirovic B, Renieris G, Ciarlo E, Le Roy D, Lepikhov K, Kattler K, Gasparoni G, Händler K, Theis H, Beyer M, van der Meer JWM, Joosten LAB, Walter J, Schultze JL, Roger T, Giamarellos-Bourboulis EJ, Schlitzer A, Netea MG. Katzmarski N, et al. Nat Immunol. 2023 Feb;24(2):371-372. doi: 10.1038/s41590-023-01426-z. Nat Immunol. 2023. PMID: 36653441 No abstract available.

Abstract

Intergenerational inheritance of immune traits linked to epigenetic modifications has been demonstrated in plants and invertebrates. Here we provide evidence for transmission of trained immunity across generations to murine progeny that survived a sublethal systemic infection with Candida albicans or a zymosan challenge. The progeny of trained mice exhibited cellular, developmental, transcriptional and epigenetic changes associated with the bone marrow-resident myeloid effector and progenitor cell compartment. Moreover, the progeny of trained mice showed enhanced responsiveness to endotoxin challenge, alongside improved protection against systemic heterologous Escherichia coli and Listeria monocytogenes infections. Sperm DNA of parental male mice intravenously infected with the fungus C. albicans showed DNA methylation differences linked to immune gene loci. These results provide evidence for inheritance of trained immunity in mammals, enhancing protection against infections.

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Comment in

Reimagining an immunological dogma.
de Candia P, Matarese G. de Candia P, et al. Nat Immunol. 2021 Nov;22(11):1355-1358. doi: 10.1038/s41590-021-01046-5. Nat Immunol. 2021. PMID: 34663980 No abstract available.
Lack of evidence for intergenerational inheritance of immune resistance to infections.
Kaufmann E, Landekic M, Downey J, Chronopoulos J, Teimouri Nezhad S, Tran K, Vinh DC, Barreiro LB, Divangahi M. Kaufmann E, et al. Nat Immunol. 2022 Feb;23(2):203-207. doi: 10.1038/s41590-021-01102-0. Epub 2022 Jan 20. Nat Immunol. 2022. PMID: 35058614 No abstract available.
Reply to: 'Lack of evidence for intergenerational inheritance of immune resistance to infections'.
Katzmarski N, Domínguez-Andrés J, Cirovic B, Renieris G, Ciarlo E, Le Roy D, Lepikhov K, Kattler K, Gasparoni G, Händler K, Theis H, Beyer M, van der Meer JWM, Joosten LAB, Walter J, Schultze JL, Roger T, Giamarellos-Bourboulis EJ, Schlitzer A, Netea MG. Katzmarski N, et al. Nat Immunol. 2022 Feb;23(2):208-209. doi: 10.1038/s41590-021-01103-z. Epub 2022 Jan 20. Nat Immunol. 2022. PMID: 35058615 No abstract available.

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References

1. Beccaloni, G. W. & Smith, V. S. Celebrations for Darwin downplay Wallace’s role. Nature 451, 1050 (2008). - DOI
1. Cubas, P., Vincent, C. & Coen, E. An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401, 157–161 (1999). - DOI
1. Luna, E., Bruce, T. J. A., Roberts, M. R., Flors, V. & Ton, J. Next-generation systemic acquired resistance. Plant Physiol. 158, 844–853 (2012). - DOI
1. Belicard, T., Jareosettasin, P. & Sarkies, P. The piRNA pathway responds to environmental signals to establish intergenerational adaptation to stress. BMC Biol. 16, 103 (2018). - DOI
1. Ferguson-Smith, A. C. & Patti, M.-E. You are what your dad ate. Cell Metab. 13, 115–117 (2011). - DOI

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[1] Beccaloni, G. W. & Smith, V. S. Celebrations for Darwin downplay Wallace’s role. Nature 451, 1050 (2008). - DOI

[2] Beccaloni, G. W. & Smith, V. S. Celebrations for Darwin downplay Wallace’s role. Nature 451, 1050 (2008). - DOI

[3] Cubas, P., Vincent, C. & Coen, E. An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401, 157–161 (1999). - DOI

[4] Cubas, P., Vincent, C. & Coen, E. An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401, 157–161 (1999). - DOI

[5] Luna, E., Bruce, T. J. A., Roberts, M. R., Flors, V. & Ton, J. Next-generation systemic acquired resistance. Plant Physiol. 158, 844–853 (2012). - DOI

[6] Luna, E., Bruce, T. J. A., Roberts, M. R., Flors, V. & Ton, J. Next-generation systemic acquired resistance. Plant Physiol. 158, 844–853 (2012). - DOI

[7] Belicard, T., Jareosettasin, P. & Sarkies, P. The piRNA pathway responds to environmental signals to establish intergenerational adaptation to stress. BMC Biol. 16, 103 (2018). - DOI

[8] Belicard, T., Jareosettasin, P. & Sarkies, P. The piRNA pathway responds to environmental signals to establish intergenerational adaptation to stress. BMC Biol. 16, 103 (2018). - DOI

[9] Ferguson-Smith, A. C. & Patti, M.-E. You are what your dad ate. Cell Metab. 13, 115–117 (2011). - DOI

[10] Ferguson-Smith, A. C. & Patti, M.-E. You are what your dad ate. Cell Metab. 13, 115–117 (2011). - DOI

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Transmission of trained immunity and heterologous resistance to infections across generations

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Transmission of trained immunity and heterologous resistance to infections across generations

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