Trained Immunity at a Glance; A Review on the Innate Immune Memory and its Potential Role in Infections, Diseases and New Therapeutic Strategies

Authors

  • Silvia Incalcaterra Faculty of Science, Radboud University, Nijmegen, The Netherlands
  • Jorge Andres Dominguez Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands

DOI:

https://doi.org/10.21467/ajgr.8.1.68-81

Abstract

Despite the existence of two different branches of immunity, innate and adaptive, it has been described that both systems are characterized by the establishment of memory responses. Indeed, it has been shown that cells belonging to the innate immune system can express a so-called “trained” memory, although it has different features from the adaptive immune memory. Adaptive memory is a long-lasting specific memory whereas innate memory involves non-specific responses which enhance the immune response during a second reinfection. However, many aspects of the trained immunity are still unclear. Metabolic and epigenetic reprogramming have been pointed as the two processes responsible for the establishment of the innate memory. Trained immunity seems to be responsible for the heterologous effect of many vaccines such as BCG, thus giving insights for the development of new therapies. Although its potential beneficial role, trained immunity could also have detrimental effects that might worsen the progress of certain diseases. The purpose of this literature review is to provide an in-depth review on the major characteristics of trained immunity, describing the main pathways at the basis of the evolution and establishment of memory in innate cells. In addition, the present review assesses the modern evidence of the impact of trained immunity in health and disease, strengthening the hypotheses that this innate memory may be considered both in the formulation of new therapeutic strategies and in the current therapeutic approaches.

Keywords:

Trained immunity, innate immunity, adaptive immunity, innate memory, vaccines, BCG

Downloads

Download data is not yet available.

References

<ol>
<li>Chaplin, D.D., <em>Overview of the immune response.</em> The Journal of allergy and clinical immunology, 2010. 125(2 Suppl 2): p. S3-S23. https://doi.org/1016/j.jaci.2009.12.980.</li>
<li>Chaplin, D.D., <em> Overview of the human immune response.</em> Journal of Allergy and Clinical Immunology, 2006. 117(2, Supplement 2): p. S430-S435. https://doi.org/10.1016/j.jaci.2005.09.034</li>
<li>Accolla, R., <em>Host Defense Mechanisms against Pathogens.</em> 7 (supplement 2): p.s5-s7. https://doi.org/10.1089/sur.2006.7.s2-5</li>
<li>Furman, D. and M.M. Davis, <em>New approaches to understanding the immune response to vaccination and infection.</em> Vaccine, 2015. 33(40): p. 5271-5281. https://doi.org/1016/j.vaccine.2015.06.117</li>
<li>Netea, M.G., et al., <em>Innate and Adaptive Immune Memory: </em><em>an</em><em> Evolutionary Continuum in the Host’s Response to Pathogens.</em> Cell Host &amp; Microbe, 2019. 25(1): p. 13-26. https://doi.org/1016/j.chom.2018.12.006</li>
<li>Dranoff, G., <em>Cytokines in cancer pathogenesis and cancer therapy.</em> Nature Reviews Cancer, 2004. 4(1): p. 11-22. https://doi.org/1038/nrc1252</li>
<li>Janeway CA Jr, T.P., Walport M, et al., <em>The front line of host defense.</em> Immunobiology: The Immune System in Health and Disease, 2001. 5th edition. https://www.ncbi.nlm.nih.gov/books/NBK10757/</li>
<li>Mathern, D.R. and P.S. Heeger, <em>Molecules Great and Small: The Complement System.</em> Clinical journal of the American Society of Nephrology : CJASN, 2015. 10(9): p. 1636-1650. https://doi.org/2215/CJN.06230614</li>
<li>Schroeder, H.W., Jr. and L. Cavacini, <em>Structure and function of immunoglobulins.</em> The Journal of allergy and clinical immunology, 2010. 125(2 Suppl 2): p. S41-S52. https://doi.org/1016/j.jaci.2009.09.046.</li>
<li>Schenten, D. and R. Medzhitov, <em>Chapter 3 - The Control of Adaptive Immune Responses by the Innate Immune System</em>, in <em>Advances in Immunology</em>, F.W. Alt, Editor. 2011, Academic Press. p. 87-124. https://doi.org/1016/B978-0-12-387664-5.00003-0.</li>
<li>Noah W. Palm, R.M., <em>Pattern recognition receptors and control of adaptive immunity.</em> Immunological Reviews, 19 December 2008. https://doi.org/10.1111/j.1600-065X.2008.00731.x</li>
<li>Beutler, B., <em>Innate immunity: an overview.</em> Molecular Immunology, 2004. 40(12): p. 845-859. https://doi.org/1016/j.molimm.2003.10.005</li>
<li>Mushegian, A. and R. Medzhitov, <em>Evolutionary perspective on innate immune recognition.</em> The Journal of cell biology, 2001. 155(5): p. 705-710. https://doi.org/1083/jcb.200107040</li>
<li>Tang, D., et al., <em>PAMPs and DAMPs: signal 0s that spur autophagy and immunity.</em> Immunological reviews, 2012. 249(1): p. 158-175. https://doi.org/1111/j.1600-065X.2012.01146.x.</li>
<li>Brubaker, S.W., et al., <em>Innate immune pattern recognition: a cell biological perspective.</em> Annual review of immunology, 2015. 33: p. 257-290. https://doi.org/1146/annurev-immunol-032414-112240.</li>
<li>Romagnolo, A.G., et al., <em>Role of Dectin-1 receptor on cytokine production by human monocytes challenged with Paracoccidioides brasiliensis.</em> 61(4): p. 222-230. https://doi.org/10.1111/myc.12725</li>
<li>Lamkanfi, M. and Vishva&nbsp;M. Dixit, <em>Mechanisms and Functions of Inflammasomes.</em> Cell, 2014. 157(5): p. 1013-1022. https://doi.org/1016/j.cell.2014.04.007.</li>
<li>Ulevitch, R.J., <em>Regulation of Receptor-Dependent Activation of the Innate Immune Response.</em> The Journal of Infectious Diseases, 2003. 187(Supplement_2): p. S351-5. https://doi.org/1086/374605</li>
<li>Goldman AS, P.B., <em>Immunology Overview.</em> Medical Microbiology, 1996. 4th edition. https://www.ncbi.nlm.nih.gov/books/NBK7795/</li>
<li>Bonilla, F.A. and H.C. Oettgen, <em>Adaptive immunity.</em> Journal of Allergy and Clinical Immunology, 2010. 125(2, Supplement 2): p. S33-S40. https://doi.org/1016/j.jaci.2009.09.017</li>
<li>Nutt, S.L., et al., <em>The generation of antibody-secreting plasma cells.</em> Nature Reviews Immunology, 2015. 15(3): p. 160-171. https://doi.org/1038/nri3795.</li>
<li>Evavold, C.L. and J.C. Kagan, <em>How Inflammasomes Inform Adaptive Immunity.</em> Journal of Molecular Biology, 2018. 430(2): p. 217-237. https://doi.org/1016/j.jmb.2017.09.019.</li>
<li>Gourbal, B., et al., <em>Innate immune memory: An evolutionary perspective.</em> 283(1): p. 21-40. https://doi.org/10.1111/imr.12647.</li>
<li>Ratajczak, W., et al., <em>Immunological memory cells.</em> Central-European journal of immunology, 2018. 43(2): p. 194-203. https://doi.org/5114/ceji.2018.77390</li>
<li>Sallusto, F., et al., <em>From Vaccines to Memory and Back.</em> Immunity, 2010. 33(4): p. 451-463. https://doi.org/1016/j.immuni.2010.10.008.</li>
<li>Ahmed, R. and D. Gray, <em>Immunological Memory and Protective Immunity: Understanding Their Relation.</em> 272(5258): p. 54-60. https://doi.org/10.1126/science.272.5258.54</li>
<li>Campos, M. and D.L. Godson, <em>The effectiveness and limitations of immune memory: understanding protective immune responses.</em> International Journal for Parasitology, 2003. 33(5): p. 655-661. https://doi.org/1016/s0020-7519(03)00066-3</li>
<li>Mulder, W.J.M., et al., <em>Therapeutic targeting of trained immunity.</em> Nature Reviews Drug Discovery, 2019. 18(7): p. 553-566. https://doi.org/1038/s41573-019-0025-4.</li>
<li>Netea, M.G. and J.W.M. van der Meer, <em>Trained Immunity: An Ancient Way of Remembering.</em> Cell Host &amp; Microbe, 2017. 21(3): p. 297-300. doi: 10.1016/j.chom.2017.02.003.</li>
<li>Buchmann, K., <em>Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals.</em> Frontiers in immunology, 2014. 5: p. 459-459. https://doi.org/3389/fimmu.2014.00459.</li>
<li>Medzhitov, R. and C.A. Janeway, <em>An ancient system of host defense.</em> Current Opinion in Immunology, 1998. 10(1): p. 12-15. https://doi.org/1016/s0952-7915(98)80024-1</li>
<li>Kurtz, J., <em>Specific memory within innate immune systems.</em> Trends in Immunology, 2005. 26(4): p. 186-192. https://doi.org/1016/j.it.2005.02.001</li>
<li>Boman, H.G., I. Nilsson, and B. Rasmuson, <em>Inducible Antibacterial Defence System in Drosophila.</em> Nature, 1972. 237(5352): p. 232-235. https://doi.org/1038/237232a0</li>
<li>Lemaitre, B., J.M. Reichhart, and J.A. Hoffmann, <em>Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms.</em> Proceedings of the National Academy of Sciences of the United States of America, 1997. 94(26): p. 14614-14619. https://doi.org/1073/pnas.94.26.14614</li>
<li>Milutinović, B. and J. Kurtz, <em>Immune memory in invertebrates.</em> Seminars in Immunology, 2016. 28(4): p. 328-342. https://doi.org/1016/j.smim.2016.05.004.</li>
<li>Reimer-Michalski, E.-M. and U. Conrath, <em>Innate immune memory in plants.</em> Seminars in Immunology, 2016. 28(4): p. 319-327. https://doi.org/1016/j.smim.2016.05.006</li>
<li>Netea, Mihai , J. Quintin, and Jos&nbsp;W.M. van&nbsp;der&nbsp;Meer, <em>Trained Immunity: A Memory for Innate Host Defense.</em> Cell Host &amp; Microbe, 2011. 9(5): p. 355-361. https://doi.org/10.1016/j.chom.2011.04.006.</li>
<li>Sun, J.C., J.N. Beilke, and L.L. Lanier, <em>Adaptive immune features of natural killer cells.</em> Nature, 2009. 457(7229): p. 557-561. https://doi.org/1038/nature07665.</li>
<li>Netea, M.G. and R. van Crevel, <em>BCG-induced protection: Effects on innate immune memory.</em> Seminars in Immunology, 2014. 26(6): p. 512-517. https://doi.org/1016/j.smim.2014.09.006.</li>
<li>Kleinnijenhuis, J., et al., <em>BCG-induced trained immunity in NK cells: Role for non-specific protection to infection.</em> Clinical Immunology, 2014. 155(2): p. 213-219. https://doi.org/1016/j.clim.2014.10.005</li>
<li>Netea, M.G., et al., <em>Trained immunity: A program of innate immune memory in health and disease.</em> Science, 2016. 352(6284): p. aaf1098. https://doi.org/1126/science.aaf1098</li>
<li>Ganeshan, K. and A. Chawla, <em>Metabolic Regulation of Immune Responses.</em> 32(1): p. 609-634. https://doi.org/10.1146/annurev-immunol-032713-120236.</li>
<li>Pearce, E.L. and E.J. Pearce, <em>Metabolic pathways in immune cell activation and quiescence.</em> Immunity, 2013. 38(4): p. 633-643. https://doi.org/1016/j.immuni.2013.04.005.</li>
<li>du Plessis, S.S., et al., <em>Oxidative phosphorylation versus glycolysis: what fuel do spermatozoa use?</em> Asian journal of andrology, 2015. 17(2): p. 230-235. https://doi.org/4103/1008-682X.135123</li>
<li>Dominguez-Andres, J. and M.G. Netea, <em>Long-term reprogramming of the innate immune system.</em> 105(2): p. 329-338. https://doi.org/10.1002/JLB.MR0318-104R.</li>
<li>Kelly, B. and L.A.J. O'Neill, <em>Metabolic reprogramming in macrophages and dendritic cells in innate immunity.</em> Cell research, 2015. 25(7): p. 771-784. https://doi.org/1038/cr.2015.68</li>
<li>O'Neill, L.A.J. and E.J. Pearce, <em>Immunometabolism governs dendritic cell and macrophage function.</em> The Journal of experimental medicine, 2016. 213(1): p. 15-23. https://doi.org/1084/jem.20151570.</li>
<li>Arts, R.J.W., L.A.B. Joosten, and M.G. Netea, <em>Immunometabolic circuits in trained immunity.</em> Seminars in Immunology, 2016. 28(5): p. 425-430. https://doi.org/1016/j.smim.2016.09.002</li>
<li>Cheng, S.-C., et al., <em>mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity.</em> 345(6204): p. 1250684. https://doi.org/10.1126/science.1250684.</li>
<li>Arts, R.J.W., et al., <em>Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity.</em> Cell Metabolism, 2016. 24(6): p. 807-819. https://doi.org/1016/j.cmet.2016.10.008.</li>
<li>Domínguez-Andrés, J., L.A.B. Joosten, and M.G. Netea, <em>Induction of innate immune memory: the role of cellular metabolism.</em> Current Opinion in Immunology, 2019. 56: p. 10-16. doi: 10.1016/j.coi.2018.09.001.</li>
<li>Yahya Sohrabi, R.G., Hannes M. Findeisen, <em>Altered Cellular Metabolism Drives Trained Immunity.</em> Trends in Endocrinology and Metabolism, 2018. 29 (9): p. 602-605. https://doi.org/1016/j.tem.2018.03.012.</li>
<li>Chen, S., et al., <em>Epigenetic regulation of macrophages: from homeostasis maintenance to host defense.</em> Cellular &amp; Molecular Immunology, 2020. 17(1): p. 36-49. <a href="https://doi.org/10.1038/s41423-019-0315-0">https://doi.org/10.1038/s41423-019-0315-0</a></li>
<li>Samuel T. Keating, A.E.-O., <em>Epigenetic and Metabolism.</em> Circulation Research, 2015. 116: p. 715-736. https://doi.org/10.1161/CIRCRESAHA.116.303936</li>
<li>Rodriguez, R.M., B. Suarez-Alvarez, and C. Lopez-Larrea, <em>Therapeutic Epigenetic Reprogramming of Trained Immunity in Myeloid Cells.</em> Trends in Immunology, 2019. 40(1): p. 66-80. https://doi.org/1016/j.it.2018.11.006.</li>
<li>Quintin, J., et al., <em>Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes.</em> Cell Host &amp; Microbe, 2012. 12(2): p. 223-232. https://doi.org/1016/j.chom.2012.06.006.</li>
<li>van der Heijden, C.D.C.C., et al., <em>Epigenetics and Trained Immunity.</em> Antioxidants &amp; redox signaling, 2018. 29(11): p. 1023-1040. https://doi.org/1089/ars.2017.7310.</li>
<li>Sánchez-Ramón, S., et al., <em>Trained Immunity-Based Vaccines: A New Paradigm for the Development of Broad-Spectrum Anti-</em><em>infectious</em> 2018. 9(2936). https://doi.org/10.3389/fimmu.2018.02936</li>
<li>Oliveira, T.L., et al., <em>Recombinant BCG strains expressing chimeric proteins derived from Leptospira protect hamsters against leptospirosis.</em> Vaccine, 2019. 37(6): p. 776-782. https://doi.org/1016/j.vaccine.2018.12.050.</li>
<li>Kleinnijenhuis, J., et al., <em>Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.</em> 109(43): p. 17537-17542. https://doi.org/10.1073/pnas.1202870109</li>
<li>Parra, M., et al., <em>Molecular Analysis of Non-Specific Protection against Murine Malaria Induced by BCG Vaccination.</em> PLOS ONE, 2013. 8(7): p. e66115. https://doi.org/1371/journal.pone.0066115</li>
<li>dos Santos, J.C., et al., <em>Non-specific effects of BCG in protozoal infections: tegumentary leishmaniasis and malaria.</em> Clinical Microbiology and Infection, 2019. 25(12): p. 1479-1483. https://doi.org/10.1016/j.cmi.2019.06.002</li>
<li>Blok, B.A., et al., <em>Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines.</em> 98(3): p. 347-356. https://doi.org/10.1189/jlb.5RI0315-096R</li>
<li>de Bree, L.C.J., et al., <em>Non-specific effects of vaccines: Current evidence and potential implications.</em> Seminars in Immunology, 2018. 39: p. 35-43. https://doi.org/10.1016/j.smim.2018.06.002</li>
<li>Babjuk, M., et al., <em>EAU Guidelines on Non-Muscle-Invasive Urothelial Carcinoma of the Bladder.</em> European Urology, 2008. 54(2): p. 303-314. https://doi.org/10.1016/j.eururo.2008.04.051</li>
<li>Mitroulis, I., et al., <em>Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.</em> Cell, 2018. 172: p. 147-161.e12. https://doi.org/10.1016/j.cell.2017.11.034</li>
<li>Gillard, G.O., et al., <em>Thy1+ Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive Lymphocytes.</em> PLOS Pathogens, 2011. 7(8): p. e1002141. https://doi.org/10.1371/annotation/b29086ef-e08d-444c-8113-18a6dd429a7c</li>
<li>Tai, L.-H., et al., <em>Perioperative Influenza Vaccination Reduces Postoperative Metastatic Disease by Reversing Surgery-Induced Dysfunction in Natural Killer Cells.</em> 19(18): p. 5104-5115. https://doi.org/10.1158/1078-0432.CCR-13-0246</li>
<li>Gyssens, I.C. and M.G. Netea, <em>Heterologous effects of vaccination and trained immunity.</em> Clinical Microbiology and Infection, 2019. 25(12): p. 1457-1458. https://doi.org/10.1016/j.cmi.2019.05.024</li>
<li>Gardiner, C.M. and K.H.G. Mills, <em>The cells that mediate innate immune memory and their functional significance in inflammatory and infectious diseases.</em> Seminars in Immunology, 2016. 28(4): p. 343-350. https://doi.org/10.1016/j.smim.2016.03.001</li>
<li>Oberbarnscheidt, M.H., et al., <em>Non-self recognition by monocytes initiates allograft rejection.</em> The Journal of clinical investigation, 2014. 124(8): p. 3579-3589. https://doi.org/1172/JCI74370</li>
<li>Ochando, J., et al., “Trained immunity in organ transplantation<em>” Am J Transplant. </em>20: 10– 18, 2020. https://doi.org/10.1111/ajt.15620</li>
<li>Zecher, D., et al., <em>An Innate Response to Allogeneic Nonself Mediated by Monocytes.</em> 183(12): p. 7810-7816. https://doi.org/10.4049/jimmunol.0902194</li>
<li>Gisterå, A. and G.K. Hansson, <em>The immunology of atherosclerosis.</em> Nature Reviews Nephrology, 2017. 13(6): p. 368-380. https://doi.org/10.1038/nrneph.2017.51</li>
<li>Libby, P., et al., Nature Reviews Disease Primers, 2019. 5(1): p. 56. https://doi.org/10.1161/CIRCRESAHA.116.308334</li>
<li>Siroon Bekkering , J.Q., Leo A.B. Joosten , Jos W.M. van der Meer , Mihai G. Netea , Niels P. Riksen, <em>Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory Cytokine Production and Foam Cell Formation via Epigenetic Reprogramming of Monocytes.</em> Arteriosclerosis, Thrombosis, and Vascular Biology, 2014. 34: p. 1731–1738. https://doi.org/10.1161/ATVBAHA.114.303887</li>
<li>van der Valk, F.M., et al., <em>Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans.</em> Circulation, 2016. 134(8): p. 611-624. https://doi.org/10.1161/CIRCULATIONAHA.116.020838</li>
<li>van Tuijl, J., et al., <em>Immunometabolism orchestrates training of innate immunity in atherosclerosis.</em> Cardiovascular Research, 2019. 115(9): p. 1416-1424. https://doi.org/10.1093/cvr/cvz107</li>
<li>Wentowski, C., N. Mewada, and N.D. Nielsen, <em>Sepsis in 2018: a review.</em> Anaesthesia &amp; Intensive Care Medicine, 2019. 20(1): p. 6-13. https://doi.org/10.1016/j.mpaic.2018.11.009</li>
<li>Bomans, K., et al., <em>Sepsis Induces a Long-Lasting State of Trained Immunity in Bone Marrow Monocytes.</em> Frontiers in immunology, 2018. 9: p. 2685-2685. https://doi.org/10.3389/fimmu.2018.02685</li>
<li>Zhang, H., et al., <em>Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88.</em> Stem cell reports, 2016. 6(6): p. 940-956. https://doi.org/10.1016/j.stemcr.2016.05.002</li>
<li>van der Meer, J.W.M., et al., <em>Trained immunity: A smart way to enhance innate immune defence.</em> Molecular Immunology, 2015. 68(1): p. 40-44. https://doi.org/10.1016/j.molimm.2015.06.019</li>
</ol>

Downloads

Published

2020-04-25

Issue

Section

Graduate Reviews

How to Cite

[1]
S. Incalcaterra and J. A. Dominguez, “Trained Immunity at a Glance; A Review on the Innate Immune Memory and its Potential Role in Infections, Diseases and New Therapeutic Strategies”, Adv. J. Grad. Res., vol. 8, no. 1, pp. 68-81, Apr. 2020.