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

Jentho E, Ruiz-Moreno C, Novakovic B, Kourtzelis I, Megchelenbrink WL, Martins R, Chavakis T, Soares MP, Kalafati L, Guerra J, Roestel F, Bohm P, Godmann M, Grinenko T, Eugster A, Beretta M, Joosten LAB, Netea MG, Bauer M, Stunnenberg HG, Weis S (2021) Trained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme. Proc Natl Acad Sci U S A 118(42), e2102698118.

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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