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Volume 11
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10.3390/biomedicines11030766
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Review

Training vs. Tolerance: The Yin/Yang of the Innate Immune System

by
Trim Lajqi
1,*,
Natascha Köstlin-Gille
1,2,
Reinhard Bauer
3,
Sotirios G. Zarogiannis
4,
Esra Lajqi
5,
Valdrina Ajeti
6,
Stefanie Dietz
1,2,
Simon A. Kranig
1,
Jessica Rühle
2,
Ardian Demaj
7,
Janine Hebel
2,
Maria Bartosova
8,
David Frommhold
9,
Hannes Hudalla
1 and
Christian Gille
1,*
1
Department of Neonatology, Heidelberg University Children’s Hospital, D-69120 Heidelberg, Germany
2
Department of Neonatology, University of Tübingen, D-72076 Tübingen, Germany
3
Institute of Molecular Cell Biology, Jena University Hospital, D-07745 Jena, Germany
4
Department of Physiology, School of Health Sciences, Faculty of Medicine, University of Thessaly, GR-41500 Larissa, Greece
5
Department of Radiation Oncology, Heidelberg University Hospital, D-69120 Heidelberg, Germany
6
Department of Pharmacy, Alma Mater Europaea—Campus College Rezonanca, XK-10000 Pristina, Kosovo
7
Faculty of Medical Sciences, University of Tetovo, MK-1200 Tetova, North Macedonia
8
Center for Pediatric and Adolescent Medicine Heidelberg, University of Heidelberg, D-69120 Heidelberg, Germany
9
Klinik für Kinderheilkunde und Jugendmedizin, D-87700 Memmingen, Germany
*
Authors to whom correspondence should be addressed.
Biomedicines 2023, 11(3), 766; https://doi.org/10.3390/biomedicines11030766
Submission received: 3 February 2023 / Revised: 26 February 2023 / Accepted: 27 February 2023 / Published: 2 March 2023
(This article belongs to the Special Issue Trained Immunity and Endotoxin Tolerance in Inflammatory Diseases)
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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 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.
Keywords: trained immunity; tolerance; inflammatory; dose; PAMPs; DAMPs; epigenetic; metabolic; signaling; diseases trained immunity; tolerance; inflammatory; dose; PAMPs; DAMPs; epigenetic; metabolic; signaling; diseases

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MDPI and ACS Style

Lajqi, T.; Köstlin-Gille, N.; Bauer, R.; Zarogiannis, S.G.; Lajqi, E.; Ajeti, V.; Dietz, S.; Kranig, S.A.; Rühle, J.; Demaj, A.; et al. Training vs. Tolerance: The Yin/Yang of the Innate Immune System. Biomedicines 2023, 11, 766. https://doi.org/10.3390/biomedicines11030766

AMA Style

Lajqi T, Köstlin-Gille N, Bauer R, Zarogiannis SG, Lajqi E, Ajeti V, Dietz S, Kranig SA, Rühle J, Demaj A, et al. Training vs. Tolerance: The Yin/Yang of the Innate Immune System. Biomedicines. 2023; 11(3):766. https://doi.org/10.3390/biomedicines11030766

Chicago/Turabian Style

Lajqi, Trim, Natascha Köstlin-Gille, Reinhard Bauer, Sotirios G. Zarogiannis, Esra Lajqi, Valdrina Ajeti, Stefanie Dietz, Simon A. Kranig, Jessica Rühle, Ardian Demaj, and et al. 2023. "Training vs. Tolerance: The Yin/Yang of the Innate Immune System" Biomedicines 11, no. 3: 766. https://doi.org/10.3390/biomedicines11030766

APA Style

Lajqi, T., Köstlin-Gille, N., Bauer, R., Zarogiannis, S. G., Lajqi, E., Ajeti, V., Dietz, S., Kranig, S. A., Rühle, J., Demaj, A., Hebel, J., Bartosova, M., Frommhold, D., Hudalla, H., & Gille, C. (2023). Training vs. Tolerance: The Yin/Yang of the Innate Immune System. Biomedicines, 11(3), 766. https://doi.org/10.3390/biomedicines11030766

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