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Review
. 2024 Apr 29:15:1393283.
doi: 10.3389/fimmu.2024.1393283. eCollection 2024.

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Eduardo López-Collazo  1   2   3 , Carlos Del Fresno  1   4
Affiliations
Review

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Eduardo López-Collazo et al. Front Immunol. .

Abstract

For decades, innate immune cells were considered unsophisticated first responders, lacking the adaptive memory of their T and B cell counterparts. However, mounting evidence demonstrates the surprising complexity of innate immunity. Beyond quickly deploying specialized cells and initiating inflammation, two fascinating phenomena - endotoxin tolerance (ET) and trained immunity (TI) - have emerged. ET, characterized by reduced inflammatory response upon repeated exposure, protects against excessive inflammation. Conversely, TI leads to an enhanced response after initial priming, allowing the innate system to mount stronger defences against subsequent challenges. Although seemingly distinct, these phenomena may share underlying mechanisms and functional implications, blurring the lines between them. This review will delve into ET and TI, dissecting their similarities, differences, and the remaining questions that warrant further investigation.

Keywords: endotoxin tolerance; innate immune memory; macrophage; monocyte; trained immunity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The laboratory of EL-C is funded by grants from Instituto de Salud Carlos III (ISCIII) and “Fondos FEDER” (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), co-funded by European Development Regional Fund “A way to achieve Europe”. Fundación Familia Alonso, Santander Bank, Real Seguros, Fundación Mutua Madrileña, Fundación Uria, Fundación Caixa, and Ayuntamiento de Madrid supported the research in EL-C’s lab. The laboratory of CF is funded by the Instituto de Salud Carlos III through the projects CP20/00106, PI21/01178 and AC23_2/00044 and co-funded by the European Union, Fundación para la Investigación Biomédica Hospital la Paz (FIBHULP - Luis Álvarez 2021), Scientific Foundation of the Spanish Association Against Cancer (IDEAS222745DELF), Fundación Familia Alonso, Comunidad de Madrid (CAM) (IND2022-BMD-23669), and Inmunotek. The Innate Immune Response group at IdiPAZ is funded by the Fortalece program (FORT23/00006) from the ISCIII.

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