Heme induces innate immunity memory

Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murin...

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Published inbioRxiv
Main Authors Jentho, Elisa, Novakovic, Boris, Ruiz-Moreno, Cristian C, Kourtzelis, Ioannis, Martins, Rui, Chavakis, Triantafyllos, Soares, Miguel P, Kalafati, Lydia, Guerra, Joel, Roestel, Franziska, Bohm, Peter, Godmann, Maren, Grinenko, Tatyana, Eugster, Anne, Beretta, Martina, Leo Ab Joosten, Netea, Mihai G, Stunnenberg, Hendrik G, Bauer, Michael, Weis, Sebastian
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 13.12.2019
Subjects
Chromatin
Epigenetics
Hematopoietic stem cells
Heme
Immunological memory
Innate immunity
Monocytes
Myeloid cells
Progenitor cells
Sepsis
Syk protein
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Summary:Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice. Heme-trainning in monocytes is associated with epigenetic and transcriptional profiles that overlap to some extent with those seen in beta-glucan-training, the prototype agonist of trained immunity. In sharp contrast to beta-glucan-induced training however, heme-training relied on activation of the Syk/JNK-pathway. Heme training in mice was associated with long-lasting expansion of myeloid-biased progenitor cells as well as with altered chromatin accessibility in hematopoietic stem and progenitor cells. Finally, heme-induced training was protective against bacterial sepsis in mice. In conclusion, we reveal that heme, a bona fide alarmin, induces innate immune memory regulating host response to infection.
DOI:10.1101/2019.12.12.874578