4.6 Review Book Chapter

Trained Immunity: Reprogramming Innate Immunity in Health and Disease

Journal

ANNUAL REVIEW OF IMMUNOLOGY, VOL 39
Volume 39, Issue -, Pages 667-693

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-102119-073855

Keywords

trained immunity; innate immune memory; epigenetics; immunometabolism; innate immune system

Categories

Funding

  1. IN-CONTROL CVON grants [CVON2012-03, CVON201827]
  2. Dutch Heart Foundation [2018-T028]
  3. European Research Council (ERC) [ERC 833247]
  4. Netherlands Organization for Scientific Research Spinoza [NWOSPI 94-212]
  5. Competitiveness Operational Program grant of the Romanian Ministry of European Funds (HINT) [P_37_762, MySMIS 103587]
  6. ERA-CVD Joint Transnational Call 2018 - Dutch Heart Foundation (JTC2018, project MEMORY) [2018T093]

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Trained immunity is a newly recognized phenomenon where cells of the innate immune system exhibit memory characteristics and enhanced responses upon secondary challenge. It explains the heterologous effects of vaccines, but can also lead to maladaptive effects in chronic inflammatory conditions.
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 result in increased protection against secondary infections. However, in chronic inflammatory conditions, trained immunity can induce maladaptive effects and contribute to hyperinflammation and progression of cardiovascular disease, autoinflammatory syndromes, and neuroinflammation. In this review we summarize the current state of the field of trained immunity, its mechanisms, and its roles in both health and disease.

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