• This record comes from PubMed

Trained Immunity as an Adaptive Branch of Innate Immunity

. 2021 Oct 01 ; 22 (19) : . [epub] 20211001

Language English Country Switzerland Media electronic

Document type Journal Article, Review

Grant support
61388971 RVO CEP Register

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.

See more in PubMed

Kumar H., Kawai T., Akira S. Pathogen recognition by the innate immune system. Int. Rev. Immunol. 2011;30:16–34. doi: 10.3109/08830185.2010.529976. PubMed DOI

Medzhitov R., Janeway C., Jr. Innate immune recognition: Mechanisms and pathways. Immunol. Rev. 2000;173:89–97. doi: 10.1034/j.1600-065X.2000.917309.x. PubMed DOI

Schroder K., Tschopp J. The inflammasomes. Cell. 2010;140:821–832. doi: 10.1016/j.cell.2010.01.040. PubMed DOI

Santoni G., Cardinali C., Morelli M.B., Santoni M., Nabissi M., Amantini C. Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J. Neuroinflammation. 2015;12:21. doi: 10.1186/s12974-015-0239-2. PubMed DOI PMC

Matzinger P. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 1994;12:991–1045. doi: 10.1146/annurev.iy.12.040194.005015. PubMed DOI

Matzinger P. The evolution of the danger theory. Interview by Lauren Constable, Commissioning Editor. Expert Rev. Clin. Immunol. 2012;8:311–317. doi: 10.1586/eci.12.21. PubMed DOI PMC

Cooper D., Eleftherianos I. Memory and specificity in the insect immune system: Current perspectives and future challenges. Front. Immunol. 2017;8:539. doi: 10.3389/fimmu.2017.00539. PubMed DOI PMC

Coustau C., Kurtz J., Moret Y. A novel mechanism of immune memory unveiled at the invertebrate-parasite interface. Trends Parasitol. 2016;32:353–355. doi: 10.1016/j.pt.2016.02.005. PubMed DOI

Kurtz J. Specific memory within innate immune systems. Trends Immunol. 2005;26:186–192. doi: 10.1016/j.it.2005.02.001. PubMed DOI

Kurtz J., Franz K. Innate defence: Evidence for memory in invertebrate immunity. Nature. 2003;425:37–38. doi: 10.1038/425037a. PubMed DOI

Conrath U., Beckers G.J., Langenbach C.J., Jaskiewicz M.R. Priming for enhanced defense. Annu. Rev. Phytopathol. 2015;53:97–119. doi: 10.1146/annurev-phyto-080614-120132. PubMed DOI

Kachroo A., Robin G.P. Systemic signaling during plant defense. Curr. Opin. Plant Biol. 2013;16:527–533. doi: 10.1016/j.pbi.2013.06.019. PubMed DOI

Palmieri B., Vadala M., Palmieri L. Immune memory: An evolutionary perspective. Hum. Vaccines Immunother. 2021;17:1604–1606. doi: 10.1080/21645515.2020.1846396. PubMed DOI PMC

Gourbal B., Pinaud S., Beckers G.J.M., Van Der Meer J.W.M., Conrath U., Netea M.G. Innate immune memory: An evolutionary perspective. Immunol. Rev. 2018;283:21–40. doi: 10.1111/imr.12647. PubMed DOI

Purvis A., Hector A. Getting the measure of biodiversity. Nature. 2000;405:212–219. doi: 10.1038/35012221. PubMed DOI

Milutinovic B., Kurtz J. Immune memory in invertebrates. Semin. Immunol. 2016;28:328–342. doi: 10.1016/j.smim.2016.05.004. PubMed DOI

Reimer-Michalski E.M., Conrath U. Innate immune memory in plants. Semin. Immunol. 2016;28:319–327. doi: 10.1016/j.smim.2016.05.006. PubMed DOI

Netea M.G., Joosten L.A., Latz E., Mills K.H., Natoli G., Stunnenberg H.G., O’Neill L.A., Xavier R.J. Trained immunity: A program of innate immune memory in health and disease. Science. 2016;352:aaf1098. doi: 10.1126/science.aaf1098. PubMed DOI PMC

Netea M.G., van der Meer J.W. Trained immunity: An ancient way of remembering. Cell Host Microbe. 2017;21:297–300. doi: 10.1016/j.chom.2017.02.003. PubMed DOI

Netea M.G., Quintin J., van der Meer J.W. Trained immunity: A memory for innate host defense. Cell Host Microbe. 2011;9:355–361. doi: 10.1016/j.chom.2011.04.006. PubMed DOI

Cao X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat. Rev. Immunol. 2016;16:35–50. doi: 10.1038/nri.2015.8. PubMed DOI

Sharma D., Kanneganti T.D. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. J. Cell Biol. 2016;213:617–629. doi: 10.1083/jcb.201602089. PubMed DOI PMC

Guo H., Callaway J.B., Ting J.P. Inflammasomes: Mechanism of action, role in disease, and therapeutics. Nat. Med. 2015;21:677–687. doi: 10.1038/nm.3893. PubMed DOI PMC

Menu P., Vince J.E. The NLRP3 inflammasome in health and disease: The good, the bad and the ugly. Clin. Exp. Immunol. 2011;166:1–15. doi: 10.1111/j.1365-2249.2011.04440.x. PubMed DOI PMC

Bekkering S., Quintin J., Joosten L.A., van der Meer J.W., Netea M.G., Riksen N.P. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler. Thromb. Vasc. Biol. 2014;34:1731–1738. doi: 10.1161/ATVBAHA.114.303887. PubMed DOI

Thorburn A.N., Macia L., Mackay C.R. Diet, metabolites, and "western-lifestyle" inflammatory diseases. Immunity. 2014;40:833–842. doi: 10.1016/j.immuni.2014.05.014. PubMed DOI

Hirano M., Das S., Guo P., Cooper M.D. The evolution of adaptive immunity in vertebrates. Adv. Immunol. 2011;109:125–157. doi: 10.1016/B978-0-12-387664-5.00004-2. PubMed DOI

Sima P., Vetvicka V. Evolution of Immune Functions. CRC Press; Boca Raton, FL, USA: 1990.

Větvicčka V., šíma P. Evolutionary Mechanisms of Defense Reactions. Birkhauser Verlag; Basel, Switzerland: Boston, MA, USA: 1998. p. 21.196 p.

Netea M.G., Dominguez-Andres J., Barreiro L.B., Chavakis T., Divangahi M., Fuchs E., Joosten L.A.B., van der Meer J.W.M., Mhlanga M.M., Mulder W.J.M., et al. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 2020;20:375–388. doi: 10.1038/s41577-020-0285-6. PubMed DOI PMC

Mack M., Schneider M.A., Moll C., Cihak J., Bruhl H., Ellwart J.W., Hogarth M.P., Stangassinger M., Schlondorff D. Identification of antigen-capturing cells as basophils. J. Immunol. 2005;174:735–741. doi: 10.4049/jimmunol.174.2.735. PubMed DOI

Denzel A., Maus U.A., Rodriguez Gomez M., Moll C., Niedermeier M., Winter C., Maus R., Hollingshead S., Briles D.E., Kunz-Schughart L.A., et al. Basophils enhance immunological memory responses. Nat. Immunol. 2008;9:733–742. doi: 10.1038/ni.1621. PubMed DOI

Ohnmacht C., Voehringer D. Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J. Immunol. 2010;184:344–350. doi: 10.4049/jimmunol.0901841. PubMed DOI

Schwartz C., Voehringer D. Basophils: Important emerging players in allergic and anti-parasite responses. Bioessays. 2011;33:423–426. doi: 10.1002/bies.201100028. PubMed DOI

Glatman Zaretsky A., Engiles J.B., Hunter C.A. Infection-induced changes in hematopoiesis. J. Immunol. 2014;192:27–33. doi: 10.4049/jimmunol.1302061. PubMed DOI PMC

Kaufmann E., Sanz J., Dunn J.L., Khan N., Mendonca L.E., Pacis A., Tzelepis F., Pernet E., Dumaine A., Grenier J.C., et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell. 2018;172:176–190.e19. doi: 10.1016/j.cell.2017.12.031. PubMed DOI

Mitroulis I., Ruppova K., Wang B., Chen L.S., Grzybek M., Grinenko T., Eugster A., Troullinaki M., Palladini A., Kourtzelis I., et al. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell. 2018;172:147–161.e12. doi: 10.1016/j.cell.2017.11.034. PubMed DOI PMC

Grainger J.R., Grencis R.K. Neutrophils worm their way into macrophage long-term memory. Nat. Immunol. 2014;15:902–904. doi: 10.1038/ni.2990. PubMed DOI

Chen F., Wu W., Millman A., Craft J.F., Chen E., Patel N., Boucher J.L., Urban J.F., Jr., Kim C.C., Gause W.C. Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion. Nat. Immunol. 2014;15:938–946. doi: 10.1038/ni.2984. PubMed DOI PMC

Bouchery T., Kyle R., Camberis M., Shepherd A., Filbey K., Smith A., Harvie M., Painter G., Johnston K., Ferguson P., et al. ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms. Nat. Commun. 2015;6:6970. doi: 10.1038/ncomms7970. PubMed DOI

Murray P.J., Wynn T.A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 2011;11:723–737. doi: 10.1038/nri3073. PubMed DOI PMC

Bistoni F., Verducci G., Perito S., Vecchiarelli A., Puccetti P., Marconi P., Cassone A. Immunomodulation by a low-virulence, agerminative variant of Candida albicans. Further evidence for macrophage activation as one of the effector mechanisms of nonspecific anti-infectious protection. J. Med. Vet. Mycol. 1988;26:285–299. doi: 10.1080/02681218880000401. PubMed DOI

Garcia-Valtanen P., Guzman-Genuino R.M., Williams D.L., Hayball J.D., Diener K.R. Evaluation of trained immunity by β-1, 3 (d)-glucan on murine monocytes in vitro and duration of response in vivo. Immunol. Cell Biol. 2017;95:601–610. doi: 10.1038/icb.2017.13. PubMed DOI PMC

Bando J.K., Colonna M. Innate lymphoid cell function in the context of adaptive immunity. Nat. Immunol. 2016;17:783–789. doi: 10.1038/ni.3484. PubMed DOI PMC

Ebbo M., Crinier A., Vely F., Vivier E. Innate lymphoid cells: Major players in inflammatory diseases. Nat. Rev. Immunol. 2017;17:665–678. doi: 10.1038/nri.2017.86. PubMed DOI

Cortez V.S., Robinette M.L., Colonna M. Innate lymphoid cells: New insights into function and development. Curr. Opin. Immunol. 2015;32:71–77. doi: 10.1016/j.coi.2015.01.004. PubMed DOI PMC

Spits H., Artis D., Colonna M., Diefenbach A., Di Santo J.P., Eberl G., Koyasu S., Locksley R.M., McKenzie A.N., Mebius R.E., et al. Innate lymphoid cells—A proposal for uniform nomenclature. Nat. Rev. Immunol. 2013;13:145–149. doi: 10.1038/nri3365. PubMed DOI

Kansler E.R., Li M.O. Innate lymphocytes-lineage, localization and timing of differentiation. Cell. Mol. Immunol. 2019;16:627–633. doi: 10.1038/s41423-019-0211-7. PubMed DOI PMC

Askenase M.H., Han S.J., Byrd A.L., Morais da Fonseca D., Bouladoux N., Wilhelm C., Konkel J.E., Hand T.W., Lacerda-Queiroz N., Su X.Z., et al. Bone-marrow-resident NK cells prime monocytes for regulatory function during infection. Immunity. 2015;42:1130–1142. doi: 10.1016/j.immuni.2015.05.011. PubMed DOI PMC

O’Leary J.G., Goodarzi M., Drayton D.L., von Andrian U.H. T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat. Immunol. 2006;7:507–516. doi: 10.1038/ni1332. PubMed DOI

Sun J.C., Beilke J.N., Lanier L.L. Adaptive immune features of natural killer cells. Nature. 2009;457:557–561. doi: 10.1038/nature07665. PubMed DOI PMC

Sun J.C., Madera S., Bezman N.A., Beilke J.N., Kaplan M.H., Lanier L.L. Proinflammatory cytokine signaling required for the generation of natural killer cell memory. J. Exp. Med. 2012;209:947–954. doi: 10.1084/jem.20111760. PubMed DOI PMC

Kleinnijenhuis J., Quintin J., Preijers F., Joosten L.A., Ifrim D.C., Saeed S., Jacobs C., van Loenhout J., de Jong D., Stunnenberg H.G., et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc. Natl. Acad. Sci. USA. 2012;109:17537–17542. doi: 10.1073/pnas.1202870109. PubMed DOI PMC

Yona S., Kim K.W., Wolf Y., Mildner A., Varol D., Breker M., Strauss-Ayali D., Viukov S., Guilliams M., Misharin A., et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013;38:79–91. doi: 10.1016/j.immuni.2012.12.001. PubMed DOI PMC

Pan W., Hao S., Zheng M., Lin D., Jiang P., Zhao J., Shi H., Yang X., Li X., Yu Y. Oat-derived β-glucans induced trained immunity through metabolic reprogramming. Inflammation. 2020;43:1323–1336. doi: 10.1007/s10753-020-01211-2. PubMed DOI

Keating S.T., Groh L., van der Heijden C., Rodriguez H., Dos Santos J.C., Fanucchi S., Okabe J., Kaipananickal H., van Puffelen J.H., Helder L., et al. The Set7 lysine methyltransferase regulates plasticity in oxidative phosphorylation necessary for trained immunity induced by β-glucan. Cell Rep. 2020;31:107548. doi: 10.1016/j.celrep.2020.107548. PubMed DOI PMC

Quintin J. Fungal mediated innate immune memory, what have we learned? Semin. Cell Dev. Biol. 2019;89:71–77. doi: 10.1016/j.semcdb.2018.05.023. PubMed DOI

Arts R.J., Novakovic B., Ter Horst R., Carvalho A., Bekkering S., Lachmandas E., Rodrigues F., Silvestre R., Cheng S.C., Wang S.Y., et al. Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. Cell Metab. 2016;24:807–819. doi: 10.1016/j.cmet.2016.10.008. PubMed DOI PMC

Mills E.L., O’Neill L.A. Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. Eur. J. Immunol. 2016;46:13–21. doi: 10.1002/eji.201445427. PubMed DOI

Di Luzio N.R., Williams D.L. Protective effect of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice. Infect. Immun. 1978;20:804–810. doi: 10.1128/iai.20.3.804-810.1978. PubMed DOI PMC

Marakalala M.J., Williams D.L., Hoving J.C., Engstad R., Netea M.G., Brown G.D. Dectin-1 plays a redundant role in the immunomodulatory activities of β-glucan-rich ligands in vivo. Microbes Infect. 2013;15:511–515. doi: 10.1016/j.micinf.2013.03.002. PubMed DOI PMC

Quintin J., Saeed S., Martens J.H.A., Giamarellos-Bourboulis E.J., Ifrim D.C., Logie C., Jacobs L., Jansen T., Kullberg B.J., Wijmenga C., et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012;12:223–232. doi: 10.1016/j.chom.2012.06.006. PubMed DOI PMC

Krahenbuhl J.L., Sharma S.D., Ferraresi R.W., Remington J.S. Effects of muramyl dipeptide treatment on resistance to infection with Toxoplasma gondii in mice. Infect. Immun. 1981;31:716–722. doi: 10.1128/iai.31.2.716-722.1981. PubMed DOI PMC

Munoz N., Van Maele L., Marques J.M., Rial A., Sirard J.C., Chabalgoity J.A. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infect. Immun. 2010;78:4226–4233. doi: 10.1128/IAI.00224-10. PubMed DOI PMC

Ribes S., Meister T., Ott M., Redlich S., Janova H., Hanisch U.K., Nessler S., Nau R. Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic mice against intracerebral Escherichia coli K1 infection. J. Neuroinflammation. 2014;11:14. doi: 10.1186/1742-2094-11-14. PubMed DOI PMC

Zhang B., Chassaing B., Shi Z., Uchiyama R., Zhang Z., Denning T.L., Crawford S.E., Pruijssers A.J., Iskarpatyoti J.A., Estes M.K., et al. Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science. 2014;346:861–865. doi: 10.1126/science.1256999. PubMed DOI PMC

Van der Meer J.W., Barza M., Wolff S.M., Dinarello C.A. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc. Natl. Acad. Sci. USA. 1988;85:1620–1623. doi: 10.1073/pnas.85.5.1620. PubMed DOI PMC

Tribouley J., Tribouley-Duret J., Appriou M. Effect of Bacillus Callmette Guerin (BCG) on the receptivity of nude mice to Schistosoma mansoni. C. R. Seances Soc. Biol. Fil. 1978;172:902–904. PubMed

Van’t Wout J.W., Poell R., van Furth R. The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice. Scand. J. Immunol. 1992;36:713–719. doi: 10.1111/j.1365-3083.1992.tb03132.x. PubMed DOI

Bistoni F., Vecchiarelli A., Cenci E., Puccetti P., Marconi P., Cassone A. Evidence for macrophage-mediated protection against lethal Candida albicans infection. Infect. Immun. 1986;51:668–674. doi: 10.1128/iai.51.2.668-674.1986. PubMed DOI PMC

Vecchiarelli A., Cenci E., Puliti M., Blasi E., Puccetti P., Cassone A., Bistoni F. Protective immunity induced by low-virulence Candida albicans: Cytokine production in the development of the anti-infectious state. Cell Immunol. 1989;124:334–344. doi: 10.1016/0008-8749(89)90135-4. PubMed DOI

Barton E.S., White D.W., Cathelyn J.S., Brett-McClellan K.A., Engle M., Diamond M.S., Miller V.L., Virgin H.W.t. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature. 2007;447:326–329. doi: 10.1038/nature05762. PubMed DOI

Arts R.J.W., Moorlag S., Novakovic B., Li Y., Wang S.Y., Oosting M., Kumar V., Xavier R.J., Wijmenga C., Joosten L.A.B., et al. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe. 2018;23:89–100.e5. doi: 10.1016/j.chom.2017.12.010. PubMed DOI

Walk J., de Bree L.C.J., Graumans W., Stoter R., van Gemert G.J., van de Vegte-Bolmer M., Teelen K., Hermsen C.C., Arts R.J.W., Behet M.C., et al. Outcomes of controlled human malaria infection after BCG vaccination. Nat. Commun. 2019;10:874. doi: 10.1038/s41467-019-08659-3. PubMed DOI PMC

Kleinnijenhuis J., Quintin J., Preijers F., Benn C.S., Joosten L.A., Jacobs C., van Loenhout J., Xavier R.J., Aaby P., van der Meer J.W., et al. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J. Innate Immun. 2014;6:152–158. doi: 10.1159/000355628. PubMed DOI PMC

Freyne B., Donath S., Germano S., Gardiner K., Casalaz D., Robins-Browne R.M., Amenyogbe N., Messina N.L., Netea M.G., Flanagan K.L., et al. Neonatal BCG vaccination influences cytokine responses to Toll-like receptor ligands and heterologous antigens. J. Infect. Dis. 2018;217:1798–1808. doi: 10.1093/infdis/jiy069. PubMed DOI PMC

Jensen K.J., Larsen N., Biering-Sorensen S., Andersen A., Eriksen H.B., Monteiro I., Hougaard D., Aaby P., Netea M.G., Flanagan K.L., et al. Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: A randomized-controlled trial. J. Infect. Dis. 2015;211:956–967. doi: 10.1093/infdis/jiu508. PubMed DOI PMC

Redelman-Sidi G., Glickman M.S., Bochner B.H. The mechanism of action of BCG therapy for bladder cancer—A current perspective. Nat. Rev. Urol. 2014;11:153–162. doi: 10.1038/nrurol.2014.15. PubMed DOI

Stewart J.H.t., Levine E.A. Role of bacillus Calmette-Guerin in the treatment of advanced melanoma. Expert Rev. Anticancer Ther. 2011;11:1671–1676. doi: 10.1586/era.11.163. PubMed DOI

Powles R.L., Russell J., Lister T.A., Oliver T., Whitehouse J.M., Malpas J., Chapuis B., Crowther D., Alexander P. Immunotherapy for acute myelogenous leukaemia: A controlled clinical study 2 1/2 years after entry of the last patient. Br. J. Cancer. 1977;35:265–272. doi: 10.1038/bjc.1977.38. PubMed DOI PMC

Villumsen M., Sorup S., Jess T., Ravn H., Relander T., Baker J.L., Benn C.S., Sorensen T.I., Aaby P., Roth A. Risk of lymphoma and leukaemia after bacille Calmette-Guerin and smallpox vaccination: A Danish case-cohort study. Vaccine. 2009;27:6950–6958. doi: 10.1016/j.vaccine.2009.08.103. PubMed DOI

Walk J., Keramati F., de Bree L.C.J., Arts R.J.W., Blok B., Netea M.G., Stunnenberg H.G., Sauerwein R.W. Controlled human malaria infection induces long-term functional changes in monocytes. Front. Mol. Biosci. 2020;7:604553. doi: 10.3389/fmolb.2020.604553. PubMed DOI PMC

Petit J., Embregts C.W.E., Forlenza M., Wiegertjes G.F. Evidence of trained immunity in a fish: Conserved features in carp macrophages. J. Immunol. 2019;203:216–224. doi: 10.4049/jimmunol.1900137. PubMed DOI PMC

Adams K., Weber K.S., Johnson S.M. Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function. Int. J. Mol. Sci. 2020;21:8462. doi: 10.3390/ijms21228462. PubMed DOI PMC

Furman D., Campisi J., Verdin E., Carrera-Bastos P., Targ S., Franceschi C., Ferrucci L., Gilroy D.W., Fasano A., Miller G.W., et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019;25:1822–1832. doi: 10.1038/s41591-019-0675-0. PubMed DOI PMC

Miura N.N., Ohno N., Aketagawa J., Tamura H., Tanaka S., Yadomae T. Blood clearance of (1-->3)-β-D-glucan in MRL lpr/lpr mice. FEMS Immunol. Med. Microbiol. 1996;13:51–57. doi: 10.1016/0928-8244(95)00083-6. PubMed DOI

Schwartz B., Vetvicka V. Review: β-glucans as effective antibiotic alternatives in poultry. Molecules. 2021;26:3560. doi: 10.3390/molecules26123560. PubMed DOI PMC

Sima P., Richter J., Vetvicka V. Glucans as new anticancer agents. Anticancer Res. 2019;39:3373–3378. doi: 10.21873/anticanres.13480. PubMed DOI

Leonhardt J., Grosse S., Marx C., Siwczak F., Stengel S., Bruns T., Bauer R., Kiehntopf M., Williams D.L., Wang Z.Q., et al. Candida albicans β-glucan differentiates human monocytes into a specific subset of macrophages. Front. Immunol. 2018;9:2818. doi: 10.3389/fimmu.2018.02818. PubMed DOI PMC

Vetvicka V., Vetvickova J. Effects of yeast-derived β-glucans on blood cholesterol and macrophage functionality. J. Immunotoxicol. 2009;6:30–35. doi: 10.1080/15476910802604317. PubMed DOI

Sima P., Vetvicka V., Vannucci L. Ambiguous role of immunity in malignant neoplasms. J. Tumor. 2020;8:560–564.

Namakula R., de Bree L.C.J., TH A.T., Netea M.G., Cose S., Hanevik K. Monocytes from neonates and adults have a similar capacity to adapt their cytokine production after previous exposure to BCG and β-glucan. PLoS One. 2020;15:e0229287. doi: 10.1371/journal.pone.0229287. PubMed DOI PMC

Moorlag S., Khan N., Novakovic B., Kaufmann E., Jansen T., van Crevel R., Divangahi M., Netea M.G. β-Glucan induces protective trained immunity against Mycobacterium tuberculosis infection: A key role for IL-1. Cell Rep. 2020;31:107634. doi: 10.1016/j.celrep.2020.107634. PubMed DOI PMC

Walachowski S., Tabouret G., Fabre M., Foucras G. Molecular analysis of a short-term model of β-glucans-trained immunity highlights the accessory contribution of GM-CSF in priming mouse macrophages response. Front. Immunol. 2017;8:1089. doi: 10.3389/fimmu.2017.01089. PubMed DOI PMC

Kalafati L., Kourtzelis I., Schulte-Schrepping J., Li X., Hatzioannou A., Grinenko T., Hagag E., Sinha A., Has C., Dietz S., et al. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell. 2020;183:771–785.e12. doi: 10.1016/j.cell.2020.09.058. PubMed DOI PMC

Isoda N., Eguchi Y., Nukaya H., Hosho K., Suga Y., Suga T., Nakazawa S., Sugano K. Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma. Hepatogastroenterology. 2009;56:437–441. PubMed

Wu L., Zhao J., Zhang X., Liu S., Zhao C. Antitumor effect of soluble β-glucan as an immune stimulant. Int. J. Biol. Macromol. 2021;179:116–124. doi: 10.1016/j.ijbiomac.2021.02.207. PubMed DOI

Geller A., Shrestha R., Yan J. Yeast-derived β-glucan in cancer: Novel uses of a traditional therapeutic. Int. J. Mol. Sci. 2019;20:3618. doi: 10.3390/ijms20153618. PubMed DOI PMC

Mourits V.P., Arts R.J.W., Novakovic B., Matzaraki V., de Bree L.C.J., Koeken V., Moorlag S., van Puffelen J.H., Groh L., van der Heijden C., et al. The role of Toll-like receptor 10 in modulation of trained immunity. Immunology. 2020;159:289–297. doi: 10.1111/imm.13145. PubMed DOI PMC

Wang J., Jin Z., Zhang W., Xie X., Song N., Lv T., Wu D., Cao Y. The preventable efficacy of β-glucan against leptospirosis. PLoS Negl. Trop. Dis. 2019;13:e0007789. doi: 10.1371/journal.pntd.0007789. PubMed DOI PMC

Vetvicka V., Fernandez-Botran R. β-Glucan and parasites. Helminthologia. 2018;55:177–184. doi: 10.2478/helm-2018-0021. PubMed DOI PMC

Dos Santos J.C., Barroso de Figueiredo A.M., Teodoro Silva M.V., Cirovic B., de Bree L.C.J., Damen M., Moorlag S., Gomes R.S., Helsen M.M., Oosting M., et al. β-glucan-induced trained immunity protects against Leishmania braziliensis infection: A crucial role for IL-32. Cell Rep. 2019;28:2659–2672.e6. doi: 10.1016/j.celrep.2019.08.004. PubMed DOI

Paris S., Chapat L., Martin-Cagnon N., Durand P.Y., Piney L., Cariou C., Bergamo P., Bonnet J.M., Poulet H., Freyburger L., et al. β-glucan as trained immunity-based adjuvants for rabies vaccines in dogs. Front. Immunol. 2020;11:564497. doi: 10.3389/fimmu.2020.564497. PubMed DOI PMC

Verwoolde M.B., van den Biggelaar R., van Baal J., Jansen C.A., Lammers A. Training of primary chicken monocytes results in enhanced pro-inflammatory responses. Vet. Sci. 2020;7:115. doi: 10.3390/vetsci7030115. PubMed DOI PMC

Verwoolde M.B., van den Biggelaar R., de Vries Reilingh G., Arts J.A.J., van Baal J., Lammers A., Jansen C.A. Innate immune training and metabolic reprogramming in primary monocytes of broiler and laying hens. Dev. Comp. Immunol. 2021;114:103811. doi: 10.1016/j.dci.2020.103811. PubMed DOI

Angulo M., Reyes-Becerril M., Cepeda-Palacios R., Angulo C. Oral administration of Debaryomyces hansenii CBS8339-β-glucan induces trained immunity in newborn goats. Dev. Comp. Immunol. 2020;105:103597. doi: 10.1016/j.dci.2019.103597. PubMed DOI

Libran-Perez M., Costa M.M., Figueras A., Novoa B. β-glucan administration induces metabolic changes and differential survival rates after bacterial or viral infection in turbot (Scophthalmus maximus) Fish Shellfish Immunol. 2018;82:173–182. doi: 10.1016/j.fsi.2018.08.005. PubMed DOI

Zhang Z., Chi H., Dalmo R.A. Trained innate immunity of fish is a viable approach in larval aquaculture. Front. Immunol. 2019;10:42. doi: 10.3389/fimmu.2019.00042. PubMed DOI PMC

Chang M.X., Zhang J. Alternative pre-mRNA splicing in mammals and teleost fish: A effective strategy for the regulation of immune responses against pathogen infection. Int. J. Mol. Sci. 2017;18:1530. doi: 10.3390/ijms18071530. PubMed DOI PMC

Escobar L.E., Molina-Cruz A., Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19) Proc. Natl. Acad. Sci. USA. 2020;117:17720–17726. doi: 10.1073/pnas.2008410117. PubMed DOI PMC

Netea M.G., Giamarellos-Bourboulis E.J., Dominguez-Andres J., Curtis N., van Crevel R., van de Veerdonk F.L., Bonten M. Trained immunity: A tool for reducing susceptibility to and the severity of SARS-CoV-2 infection. Cell. 2020;181:969–977. doi: 10.1016/j.cell.2020.04.042. PubMed DOI PMC

Geller A., Yan J. Could the induction of trained immunity by β-glucan serve as a defense against COVID-19? Front. Immunol. 2020;11:1782. doi: 10.3389/fimmu.2020.01782. PubMed DOI PMC

Bono C., Martinez A., Megias J., Gozalbo D., Yanez A., Gil M.L. Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism. mBio. 2020;11:e00781-20. doi: 10.1128/mBio.00781-20. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...