Volume 35, No 11, Nov 2025

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 35 Issue 11, November 2025: 792-802   |  Open Access

REVIEW ARTICLE

Trained immunity: induction of an inflammatory memory in disease

Titus Schlüter¹ , Yuri van Elsas¹ , Bram Priem¹ , Athanasios Ziogas^1,2 , Mihai G. Netea^1,3,*

¹Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
²Department of Cell Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands
³Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
Correspondence: Mihai G. Netea(mihai.netea@radboudumc.nl)

The innate immune system adapts its behavior based on previous insults, mounting an enhanced response upon re-exposure. Hematopoietic progenitors in the bone marrow and peripheral innate immune cells can undergo epigenetic and metabolic reprogramming, establishing an innate immune memory known as trained immunity. The concept of trained immunity recently gained relevance in our understanding of how innate immunity is regulated in various diseases. This review explores the role of trained immunity in infections, autoimmune disease, cardiovascular disease, cancer, and neurodegenerative disease. We discuss how trained immunity can provide heterologous protection against infections, as it has been induced for decades by the Bacillus Calmette Guérin vaccine, how it can help counteract immunosuppression, and how it can be inappropriately induced leading to chronic inflammation. By understanding how trained immunity is involved in processes leading to health and disease, novel therapeutic strategies can be developed.

https://doi.org/10.1038/s41422-025-01171-y

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