Trained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme

E Jentho; C Ruiz-Moreno; B Novakovic; I Kourtzelis; WL Megchelenbrink; R Martins; T Chavakis; MP Soares; L Kalafati; J Guerra; F Roestel; P Bohm; M Godmann; T Grinenko; A Eugster; M Beretta; LAB Joosten; MG Netea; M Bauer; HG Stunnenberg; S Weis

Journal article

Trained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme

E Jentho, C Ruiz-Moreno, B Novakovic, I Kourtzelis, WL Megchelenbrink, R Martins, T Chavakis, MP Soares, L Kalafati, J Guerra, F Roestel, P Bohm, M Godmann, T Grinenko, A Eugster, M Beretta, LAB Joosten, MG Netea, M Bauer, HG Stunnenberg Show all

Proceedings of the National Academy of Sciences of the United States of America | Published : 2021

DOI: 10.1073/pnas.2102698118

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Abstract

Trained immunity defines long-lasting adaptations of innate immunity based on transcriptional and epigenetic modifications of myeloid cells and their bone marrow progenitors [M. Divangahi et al., Nat. Immunol. 22, 2–6 (2021)]. Innate immune cells, however, do not exclusively differentiate between foreign and self but also react to host-derived molecules referred to as alarmins. Extracellular “labile” heme, released during infections, is a bona fide alarmin promoting myeloid cell activation [M. P. Soares, M. T. Bozza, Curr. Opin. Immunol. 38, 94–100 (2016)]. Here, we report that labile heme is a previously unrecognized inducer of trained immunity that confers long-term regulation of lineage s..

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University of Melbourne Researchers

Boris Novakovic Author

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Epigenetic remodelling of neonatal and maternal monocytes in pregnancy Epigenetic remodelling of neonatal and maternal monocytes in pregnancy

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Awarded by Center for Sepsis Control and Care

Funding Acknowledgements

We thank Dr. David L. Williams, Ph.D. from the Quillen College of Medicine East Tennessee State University for providing the p-glucan used in this study. We also thank Maziar Divangahi, Ph.D. from the McGill University Montreal, Canada, for his insightful comments on the manuscript. J.G., M. Bauer, and S.W. were supported by the Integrated Research and Treatment Center-Center for Sepsis Control and Care (CSCC) at the Jena University Hospital. The CSCC is funded by the German Ministry of Education and Research (BMBF No. 01EO1502) . M. Bauer and E.J. were sup-ported by Deutsche Forschungsgemeinschaft (DFG) Grant GRK 1715/2. E.J., M.P.S., M. Bauer, and S.W. are currently funded by the DFG under Germanys Excellence Strategy-EXC 2051-Project Identification 390713860. S.W. is cur-rently funded by DFG Project No. WE 4971/6-1 and BMBF Project No. 01EN2001. T.C. was supported by a grant from the DFG (SFB/TRR 127, Project A3) . B.N. is supported by an National Health and Medical Research Council (NHMRC) (Australia) Investigator Grant (No. 1173314) . M. Bauer was sup-ported by the DFG FOR 1738. M.G.N. is supported by a European Research Council Advanced Grant (No. 833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research. W.L.M. is supported by the Italian National Operational Programme on Research 2014 to 2020 (PON AIM 1859703-2) : PON Ricerca e Innovazione 2014 to 2020-Azione I.2-D.D. n.407, 27.02.2018 "Attraction and International Mobility"-Line 2 (Researchers Attraction) . C.R.-M. is supported by the European Union's Horizon 2020 Skodowska-Curie Actions (Project AiPBAND) under Grant No. 76428, and H.G.S. is supported by the Princess Maxima Center and a ZonMW Grant No. 91216061. We are part of the International Trained Immunity (INTRIM) consortium.