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REVIEW ARTICLE

Trained immunity of M1-like foamy macrophages: A key role of human endogenous retrovirus K102 particles

Marian P. Laderoute1,2*
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1 M. Villa Health & Wellness Center, The Villages, Florida, United States of America
2 Independent Researcher, Gatineau, Quebec, Canada
Global Translational Medicine, 025370071 https://doi.org/10.36922/GTM025370071
Received: 9 September 2025 | Revised: 23 January 2026 | Accepted: 10 February 2025 | Published online: 26 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Trained immunity (TI) involves foam-cell formation in M1-like macrophages, relies on glycolysis for energy and is associated with epigenetic changes that improve accessibility to innate immunity genes. However, the mechanisms by which TI reduces all-cause mortality remain poorly defined. This review provides novel insights into the role of the protector foamy retrovirus, human endogenous retrovirus K102 (HERV-K102) located at 1q22, in generating M1-like foamy macrophages (FM) and creating TI. Remarkably, the involvement of HERV-K102 particles can help explain how TI activation can resolve or prevent infections and chronic diseases resulting in negative excess all-cause mortality. This is possible since the failed release of HERV-K102 particles from FM indicates the dysfunction of M1-like macrophages, a condition known to cause chronic diseases termed the immunosenescence of macrophages (ISM). Firstly, HERV-K102 particle production in activated macrophages causes the accumulation of high levels of these particles in vacuoles, generating the foam intrinsic to TI. These particles are then released on day 6/7 by lysis. Released protector particles launch a multi-faceted protection systemically within the host, including the all-important interferon response and the activation of innate T and B cells against the HERV-K102 envelope protein (Env). This review reveals for the first time that TI memory involves genomic modification (integration of HERV-K102) associated with protection. It also explains how HERV-K102 particles released from FM may contribute not only to sterilizing immunity and herd immunity, but also to the reversal of ISM associated with TI induction, which improves all-cause mortality.

Keywords
Trained immunity
Foamy macrophage
Human endogenous retrovirus K102
Alpha-fetoprotein
Immunosenescence of macrophages
Pandemic response
HERV K-102
Funding
None.
Conflict of interest
The author declares no competing interests.
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Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
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