Trained immunity: mechanisms in vaccination and infection

Radboud University Medical Center and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands



Research topic

The innate arm of the immune system has been generally regarded as primitive and non-specific and, in contrast to adaptive immunity, not to possess memory. A growing body of evidence demonstrated recently that innate immunity has an important capacity to adapt, a de facto innate immune memory. Our group proposed the term trained immunity, and demonstrated its role for the broad non-specific protection against infections.

Although the phenomenon of trained innate immunity (TRIM) is undoubtedly beneficial in the context of recurrent infections and vaccination, it might be detrimental in the context of chronic inflammatory disorders that are driven by chronic activation of the innate immune system. We have developed several models of trained immunity in-vitro, using both entire microorganisms (e.g. C. albicans, BCG) or purified microbial components (e.g. –glucan, MDP). In addition, we demonstrated the capacity of these training stimuli to induce non-specific protection to infection in murine models. Finally, we have shown that certain vaccinations in humans, such as BCG vaccination, can induce long-term changes in monocytes of vaccinated individuals, and that this induces protection against unrelated pathogens.

Our groups aims to investigate several important aspects regarding trained immunity:

  • We work towards identification of the interplay between immunological signaling, changes in cellular metabolism, and epigenetic reprogramming, necessary for the induction of an efficient trained immunity response
  • We want to understand variability of trained immunity responses induced by vaccination at a population level
  • We perform functional studies to potentiate trained immunity responses, and thus improve the efficacy of vaccines.

Through the combination of these approaches, we aim that in the coming years there will be improved understanding of the pathophysiology of infections and immune-mediated diseases, and this will contribute to novel ways to diagnose, prevent and treat diseases.

Group members

  • Mihai Netea, MD, PhD, professor in experimental internal medicine
  • Leo A.B. Joosten, PhD, professor in inflammatory diseases
  • Reinout van Crevel, MD, PhD, professor in global health
  • Jos W.M. van der Meer, MD, PhD, professor of internal medicine
  • Rob Arts, MD, PhD student
  • Bas Blok, MD, PhD student
  • Simone Moorlag, MD, PhD student
  • Charlotte de Bree, MD, PhD student
  • Valerie Koeken, MD, PhD student
  • Vera Mourits, MD, PhD student 

Selected Publications

Financial support

  • ERC Consolidator Grant
  • Spinoza Grant of the Netherlands Organization for Scientific Research
  • Horizon 2020 REPROGRAM
  • Radboud University