Trained Immunity and Endotoxin Tolerance in Inflammatory Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 5081

Special Issue Editors

Department of Neonatology, Heidelberg University Children’s Hospital, Heidelberg, Germany
Interests: innate immunity; microglia; neutrophils; trained immunity; signaling; metabolism; epigenetics; endotoxin tolerance; inflammation
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Guest Editor
Department of Neonatology, Heidelberg University Children’s Hospital, Heidelberg, Germany
Interests: innate immunity; MDSC; T cells; neonatology; tolerance; sepsis; infectious diseases; trained immunity

E-Mail Website
Guest Editor
Department of Neonatology, Heidelberg University Children’s Hospital, Heidelberg, Germany
Interests: innate immunity; cell recruitment; neutrophils; sepsis; trained immunity; infectious diseases; inflammation; endotoxin tolerance

Special Issue Information

Dear Colleagues,

Innate immune cells have been shown to be able to articulate non-specific memory-like responses known as trained immunity (or innate memory; abb. TRIM), manifested with increased responsiveness against secondary pathogenic insults. Contrary to trained immunity, endotoxin tolerance is a well-known immune reaction characterized by declined responsiveness and increased repairing/anti-inflammatory reactions. Both of these opposing adaptive features of the innate immune system are shaped by different external and internal stressors, promoted mainly by epigenetic changes (including histone methylation or acetylation) with resulting changes in metabolism (glycolysis, glutaminolysis, the accumulation of fumarate, fatty acid oxidation, or itaconate pathway) and mediated particularly by the phosphoinositide 3-kinase (PI3K)/mechanistic target of the rapamycin (mTOR) pathway. Recent advances have revealed that trained memory as well as tolerance may alter several cellular functions such as migration, phagocytosis, killing abilities, and anti-microbial properties. This then has a major impact on the progression or suppression of different inflammatory diseases (i.e., allergies, atherosclerosis, asthma, obesity, sepsis, autoimmune diseases, transplant rejection, multi-system inflammatory syndrome (COVID-19)). The inappropriate induction of one of these antagonistic adaptive manners may result in maladaptive reactions which trigger life-threating events. As such, we invite all the colleagues to submit their findings in this Special Issue to further provide more insights on the role of the trained immunity and tolerance development in inflammatory disorders.  

Dr. Trim Lajqi
Dr. Christian Gille
Dr. Hannes Hudalla
Guest Editors

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Keywords

  • innate memory
  • tolerance
  • signaling
  • metabolism
  • epigenetics
  • inflammatory diseases

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Published Papers (1 paper)

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Review

32 pages, 2193 KiB  
Review
Training vs. Tolerance: The Yin/Yang of the Innate Immune System
by Trim Lajqi, Natascha Köstlin-Gille, Reinhard Bauer, Sotirios G. Zarogiannis, Esra Lajqi, Valdrina Ajeti, Stefanie Dietz, Simon A. Kranig, Jessica Rühle, Ardian Demaj, Janine Hebel, Maria Bartosova, David Frommhold, Hannes Hudalla and Christian Gille
Biomedicines 2023, 11(3), 766; https://doi.org/10.3390/biomedicines11030766 - 2 Mar 2023
Cited by 14 | Viewed by 4456
Abstract
For almost nearly a century, memory functions have been attributed only to acquired immune cells. Lately, this paradigm has been challenged by an increasing number of studies revealing that innate immune cells are capable of exhibiting memory-like features resulting in increased responsiveness to [...] Read more.
For almost nearly a century, memory functions have been attributed only to acquired immune cells. Lately, this paradigm has been challenged by an increasing number of studies revealing that innate immune cells are capable of exhibiting memory-like features resulting in increased responsiveness to subsequent challenges, a process known as trained immunity (known also as innate memory). In contrast, the refractory state of endotoxin tolerance has been defined as an immunosuppressive state of myeloid cells portrayed by a significant reduction in the inflammatory capacity. Both training as well tolerance as adaptive features are reported to be accompanied by epigenetic and metabolic alterations occurring in cells. While training conveys proper protection against secondary infections, the induction of endotoxin tolerance promotes repairing mechanisms in the cells. Consequently, the inappropriate induction of these adaptive cues may trigger maladaptive effects, promoting an increased susceptibility to secondary infections—tolerance, or contribute to the progression of the inflammatory disorder—trained immunity. This review aims at the discussion of these opposing manners of innate immune and non-immune cells, describing the molecular, metabolic and epigenetic mechanisms involved and interpreting the clinical implications in various inflammatory pathologies. Full article
(This article belongs to the Special Issue Trained Immunity and Endotoxin Tolerance in Inflammatory Diseases)
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