Defining trained immunity and its role in health and disease

  • Nat Rev Immunol. 2020 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6.
Mihai G Netea  1  2  3 ,  Jorge Domínguez-Andrés  4  5 ,  Luis B Barreiro  6  7  8 ,  Triantafyllos Chavakis  9  10 ,  Maziar Divangahi  11  12  13 ,  Elaine Fuchs  14 ,  Leo A B Joosten  4  5 ,  Jos W M van der Meer  4  5 ,  Musa M Mhlanga  15  16 ,  Willem J M Mulder  17  18  19 ,  Niels P Riksen  4  5 ,  Andreas Schlitzer  20 ,  Joachim L Schultze  21 ,  Christine Stabell Benn  22 ,  Joseph C Sun  23  24  25 ,  Ramnik J Xavier  26  27 ,  Eicke Latz  28  29  30
Affiliations
  • 1. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands. [email protected].
  • 2. Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands. [email protected].
  • 3. Department of Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. [email protected].
  • 4. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • 5. Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
  • 6. Department of Genetics, CHU Sainte-Justine Research Centre, Montreal, QC, Canada.
  • 7. Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
  • 8. Genetics Section, Department of Medicine, The University of Chicago, Chicago, IL, USA.
  • 9. Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany.
  • 10. Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
  • 11. Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.
  • 12. Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
  • 13. McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada.
  • 14. Howard Hughes Medical Institute, Robin Chemers Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA.
  • 15. Division of Chemical and Systems Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
  • 16. Gene Expression and Biophysics Unit, Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal.
  • 17. Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 18. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 19. Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands.
  • 20. Myeloid Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
  • 21. Department of Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
  • 22. Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
  • 23. Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 24. Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 25. Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA.
  • 26. Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • 27. Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • 28. Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany. [email protected].
  • 29. Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA. [email protected].
  • 30. German Center for Neurodegenerative Diseases, Bonn, Germany. [email protected].
PMID: 32132681 DOI: 10.1038/s41577-020-0285-6
Abstract

Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.