Induction of Trained Immunity Protects Neonatal Mice Against Microbial Sepsis by Boosting Both the Inflammatory Response and Antimicrobial Activity

References

• Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385:430–440. doi:10.1016/S0140-6736(14)61698-6
   PubMed Web of Science ®Google Scholar
• Raymond SL, Stortz JA, Mira JC, Larson SD, Wynn JL, Moldawer LL. Immunological defects in neonatal sepsis and potential therapeutic approaches. Front Pediatr. 2017;5:14. doi:10.3389/fped.2017.00014
   PubMed Web of Science ®Google Scholar
• Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390:1770–1780. doi:10.1016/S0140-6736(17)31002-4
   PubMed Web of Science ®Google Scholar
• Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr. 2016;28:135–140. doi:10.1097/MOP.0000000000000315
   PubMed Web of Science ®Google Scholar
• PrabhuDas M, Adkins B, Gans H, et al. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. 2011;12:189–194. doi:10.1038/ni0311-189
   PubMed Web of Science ®Google Scholar
• Zaghouani H, Hoeman CM, Adkins B. Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol. 2009;30:585–591. doi:10.1016/j.it.2009.09.002
   PubMed Web of Science ®Google Scholar
• Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, Levy F. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity. 2017;46:350–363. doi:10.1016/j.immuni.2017.03.009
   PubMed Web of Science ®Google Scholar
• Wynn JL, Scumpia PO, Winfield RD, et al. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood. 2008;112:1750–1758. doi:10.1182/blood-2008-01-130500
   PubMed Web of Science ®Google Scholar
• Kollmann TR, Crabtree J, Rein-Weston A, et al. Neonatal innate TLR-mediated responses are distinct from those of adults. J Immunol. 2009;183:7150–7160. doi:10.4049/jimmunol.0901481
   PubMed Web of Science ®Google Scholar
• Zhang Q, Coveney AP, Yu S, et al. Inefficient antimicrobial functions of innate phagocytes render infant mice more susceptible to bacterial infection. Eur J Immunol. 2013;43:1322–1332. doi:10.1002/eji.201243077
   PubMed Web of Science ®Google Scholar
• Kan B, Razzaghian HR, Lavoie PM. An immunological perspective on neonatal sepsis. Trends Mol Med. 2016;22:290–302. doi:10.1016/j.molmed.2016.02.001
   PubMed Web of Science ®Google Scholar
• Netea MG, Joosten LA, Latz E, et al. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352:aaf1098. doi:10.1126/science.aaf1098
   PubMed Web of Science ®Google Scholar
• Quintin J, Saeed S, Martens JH, 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 Web of Science ®Google Scholar
• Saeed S, Quintin J, Kerstens HH, et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science. 2014;345:1251086. doi:10.1126/science.1251086
   PubMed Web of Science ®Google Scholar
• Bekkering S, Arts RJW, Novakovic B, et al. Metabolic induction of trained immunity through the mevalonate pathway. Cell. 2018;172:135–146. doi:10.1016/j.cell.2017.11.025
   PubMed Web of Science ®Google Scholar
• Cheng SC, Scicluna BP, Arts RJ, et al. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nat Immunol. 2016;17:406–413. doi:10.1038/ni.3398
   PubMed Web of Science ®Google Scholar
• Arts RJW, Carvalho A, La Rocca C, et al. Immunometabolic pathways in BCG-induced trained immunity. Cell Rep. 2016;17:2562–2571. doi:10.1016/j.celrep.2016.11.011
   PubMed Web of Science ®Google Scholar
• Kaufmann E, Sanz J, Dunn JL, et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell. 2018;172:176–190. doi:10.1016/j.cell.2017.12.031
   PubMed Web of Science ®Google Scholar
• Arts RJW, Moorlag S, Novakovic 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. doi:10.1016/j.chom.2017.12.010
   PubMed Web of Science ®Google Scholar
• Fanucchi S, Domínguez-Andrés J, Joosten LAB, Netea MG, Mhlanga MM. The intersection of epigenetics and metabolism in trained immunity. Immunity. 2021;54:32–43. doi:10.1016/j.immuni.2020.10.011
   PubMed Web of Science ®Google Scholar
• Cheng SC, Quintin J, Cramer RA, et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014;345:1250684. doi:10.1126/science.1250684
   PubMed Web of Science ®Google Scholar
• Arts RJ, Novakovic B, Ter Horst R, 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 Web of Science ®Google Scholar
• Penkov S, Mitroulis I, Hajishengallis G, Chavakis T. Immunometabolic crosstalk: an ancestral principle of trained immunity? Trends Immunol. 2019;40:1–11. doi:10.1016/j.it.2018.11.002
   PubMed Web of Science ®Google Scholar
• Bekkering S, Domínguez-Andrés J, Joosten LAB, Riksen NP, Netea MG. Trained immunity: reprogramming innate immunity in health and disease. Annu Rev Immunol. 2021;39:667–693. doi:10.1146/annurev-immunol-102119-073855
   PubMed Web of Science ®Google Scholar
• Wynn JL, Scumpia PO, Delano MJ, et al. Increased mortality and altered immunity in neonatal sepsis produced by generalized peritonitis. Shock. 2007;28:675–683. doi:10.1097/shk.0b013e3180556d09
   PubMed Web of Science ®Google Scholar
• O’Brien GC, Wang JH, Redmond HP. Bacterial lipoprotein induces resistance to Gram-negative sepsis in TLR4-deficient mice via enhanced bacterial clearance. J Immunol. 2005;174:1020–1026. doi:10.4049/jimmunol.174.2.1020
   PubMed Web of Science ®Google Scholar
• Buckley JM, Liu JH, Li CH, et al. Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function. J Immunol. 2011;187:4293–4299. doi:10.4049/jimmunol.1003872
   PubMed Web of Science ®Google Scholar
• Liu J, Buckley JM, Redmond HP, Wang JH. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance. J Immunol. 2010;184:5802–5808. doi:10.4049/jimmunol.0904127
   PubMed Web of Science ®Google Scholar
• Coveney AP, Wang W, Kelly J, et al. Myeloid-related protein 8 induces self-tolerance and cross-tolerance to bacterial infection via TLR4- and TLR2-mediated signal pathways. Sci Rep. 2015;5:13694. doi:10.1038/srep13694
   PubMed Web of Science ®Google Scholar
• Wang JH, Doyle M, Manning BJ, et al. Cutting edge: bacterial lipoprotein induces endotoxin-independent tolerance to septic shock. J Immunol. 2003;170:14–18. doi:10.4049/jimmunol.170.1.14
   PubMed Web of Science ®Google Scholar
• Zhou HT, Coveney AP, Wu M, et al. Activation of both TLR and NOD signaling synergizes to confer host innate immunity-mediated protection against microbial infection. Front Immunol. 2019;9:3082. doi:10.3389/fimmu.2018.03082
   PubMed Web of Science ®Google Scholar
• Savina A, Jancic C, Hugues S, et al. NOX2 controls phagosomal pH to regulate antigen processing during cross presentation by dendritic cells. Cell. 2006;126:205–218. doi:10.1016/j.cell.2006.05.035
   PubMed Web of Science ®Google Scholar
• Hmama Z, Sendide K, Talal A, Garcia R, Dobos K, Reiner NE. Quantitative analysis of phagolysosome fusion in intact cells: inhibition by mycobacterial lipoarabinomannan and rescue by an 1alpha, 25-dihydroxyvitamin D3 phosphoinositide 3-kinase pathway. J Cell Sci. 2004;117:2131–2140. doi:10.1242/jcs.01072
   PubMed Web of Science ®Google Scholar
• Keating ST, Groh L, Thiem K, et al. Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein. J Mol Med. 2020;98:819–831. doi:10.1007/s00109-020-01915-w
   PubMed Web of Science ®Google Scholar
• Chen W, Zhao S, Ita M, et al. An early neutrophil recruitment into the infectious site is critical for bacterial lipoprotein tolerance-afforded protection against microbial sepsis. J Immunol. 2020;204:408–417. doi:10.4049/jimmunol.1801602
   PubMed Web of Science ®Google Scholar
• Alves-Filho JC, Sonego F, Souto FO, et al. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010;16:708–712. doi:10.1038/nm.2156
   PubMed Web of Science ®Google Scholar
• Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007;449:819–826. doi:10.1038/nature06246
   PubMed Web of Science ®Google Scholar
• Ishii KJ, Koyama S, Nakagawa A, Coban C, Akira S. Host innate immune receptors and beyond: making sense of microbial infections. Cell Host Microbe. 2008;3:352–363. doi:10.1016/j.chom.2008.05.003
   PubMed Web of Science ®Google Scholar
• Blander JM, Medzhitov R. Regulation of phagosome maturation by signals from toll-like receptors. Science. 2004;304:1014–1018. doi:10.1126/science.1096158
   PubMed Web of Science ®Google Scholar
• Kinchen JM, Ravichandran KS. Phagosome maturation: going through the acid test. Nat Rev Mol Cell Biol. 2008;9:781–795. doi:10.1038/nrm2515
   PubMed Web of Science ®Google Scholar
• Liu J, Xiang J, Li X, et al. NF-κB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection. Sci Rep. 2017;7:40418. doi:10.1038/srep40418
   PubMed Web of Science ®Google Scholar
• Bekkering S, Blok BA, Joosten LA, Riksen NP, van Crevel R, Netea MG. In vitro experimental model of trained innate immunity in human primary monocytes. Clin Vaccine Immunol. 2016;23:926–933. doi:10.1128/CVI.00349-16
   PubMed Web of Science ®Google Scholar
• Wang JH, Doyle M, Manning BJ, Wu QD, Blankson S, Redmond HP. Induction of bacterial lipoprotein tolerance is associated with suppression of toll-like receptor 2 expression. J Biol Chem. 2002;277:36068–36075. doi:10.1074/jbc.M205584200
   PubMed Web of Science ®Google Scholar
• Buckley JM, Wang JH, Redmond HP. Cellular reprogramming by gram-positive bacterial components: a review. J Leukoc Biol. 2006;80:731–741. doi:10.1189/jlb.0506312
   PubMed Web of Science ®Google Scholar
• Domínguez-Andrés J, Joosten LA, Netea MG. Induction of innate immune memory: the role of cellular metabolism. Curr Opin Immunol. 2019;56:10–16.
   PubMed Web of Science ®Google Scholar