Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Innate immune memory, trained immunity and nomenclature clarification

Nature Immunology volume 24, pages 1393–1394 (2023)Cite this article

Subjects

Trained innate immunity (TRIM) is a newly emerging field of study that is of focal importance in immunology. Defined as an enhanced immune responsiveness of innate immune cells to a future challenge owing to memory of a prior encounter, TRIM existed as a latent, yet ignored, concept even before it was coined as such and systematized as a new field1,2. Epidemiological studies indicating antigen-agnostic protective effects of certain vaccines unrelated to their target disease, experimental animal studies showing lymphocyte-independent enhanced resistance to secondary infection, and evidence of memory-based broad protection against reinfection in invertebrates and plants (reviewed in refs. 1,3) were largely overlooked in the face of the concept that immunological memory was the exclusive prerogative of adaptive immunity. Given the importance of immune memory for host defense and survival, it is now thought that trained innate immunity evolved first, as an epigenetically based memory devoid of specificity, before antigen-specific immunological memory developed in jawed vertebrates, leading later to the acquisition of recombination-activating genes and hence the ability to generate a diverse repertoire of antigen-specific receptors4.

Precise immunological nomenclature has always been a formidable challenge, given the complexity and plasticity of the immune response5, and this is particularly true for a newly emerged area of immunological research. Despite earlier efforts to clarify key terms in the field2, it may still be unclear whether TRIM is different from persistent innate immune activation or even from innate immune memory. The latter is so intimately related to TRIM that the two terms are often used interchangeably, especially given that TRIM represents a functional consequence of de facto innate immune memory. Although this is acceptable, for precision where this is warranted, we think that both terms are necessary in the immunological literature.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Induction of innate immune memory that leads to trained immune response after restimulation.

References

  1. Netea, M. G., Quintin, J. & van der Meer, J. W. Cell Host Microbe 9, 355–361 (2011).

    Article  CAS  PubMed  Google Scholar 

  2. Divangahi, M. et al. Nat. Immunol. 22, 2–6 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Penkov, S., Mitroulis, I., Hajishengallis, G. & Chavakis, T. Trends Immunol. 40, 1–11 (2019).

    Article  CAS  PubMed  Google Scholar 

  4. Netea, M. G., Schlitzer, A., Placek, K., Joosten, L. A. B. & Schultze, J. L. Cell Host Microbe 25, 13–26 (2019).

    Article  CAS  PubMed  Google Scholar 

  5. Mantovani, A. Nat. Immunol. 17, 215–216 (2016).

    Article  CAS  PubMed  Google Scholar 

  6. de Laval, B. et al. Cell Stem Cell 26, 657–674.E658 (2020).

    Article  PubMed  Google Scholar 

  7. Li, X. et al. Cell 185, 1709–1727.e1718 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kalafati, L. et al. Cell 183, 771–785.e712 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    George Hajishengallis

  2. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands

    Mihai G. Netea

  3. Department of Immunology and Metabolism, Life and Medical Science Institute, University of Bonn, Bonn, Germany

    Mihai G. Netea

  4. Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany

    Triantafyllos Chavakis

Authors
  1. George Hajishengallis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mihai G. Netea
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Triantafyllos Chavakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Hajishengallis.

Ethics declarations

Competing interests

M.G.N. is a scientific founder of Lemba, TTxD and Biotrip. The other authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hajishengallis, G., Netea, M.G. & Chavakis, T. Innate immune memory, trained immunity and nomenclature clarification. Nat Immunol 24, 1393–1394 (2023). https://doi.org/10.1038/s41590-023-01595-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41590-023-01595-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing