Inntate immune training

A characteristic hallmark of myeloid cell activation is the development of trained immunity, specified as long-lasting adaptations based on transcriptional and epigenetic modifications. In vivo this has been shown to be maintained by rerouting of hematopoiesis. Our group is working on innate immune memory development in response to the exposure of host derived molecules referred to as danger associated molecular patterns in different species including mice, naked mole rats and humans. We consider understanding of potential evolutionary differences will provide new perceptions of the regulatory mechanisms controlling the balance of the innate immune response in general. Recently we found that the iron containing porphyrin heme is a previously unrecognized trained immunity inducer promoting resistance to bacterial infection in mice. This goes along with extensive long-lasting epigenetic memory in hematopoietic stem cells provoking drastic changes in the transcription factor binding landscape of myeloid progenitor cells and is potentially evoked by sustained activity of Nfix, Runx1 and Nfe2l2 and dissociation of the transcriptional repressor Bach2. We are currently following up on these findings.

Five most important publications

Divangahi M, Aaby P, Khader SA, Barreiro LB, Bekkering S, Chavakis T, van Crevel R, Curtis N, DiNardo AR, Dominguez-Andres J, Duivenvoorden R, Fanucchi S, Fayad Z, Fuchs E, Hamon M, Jeffrey KL, Khan N, Joosten LAB, Kaufmann E, Latz E, Matarese G, van der Meer JWM, Mhlanga M, Moorlag SJCFM, Mulder WJM, Naik S, Novakovic B, O'Neill L, Ochando J, Ozato K, Riksen NP, Sauerwein R, Sherwood ER, Schlitzer A, Schultze JL, Sieweke MH, Benn CS, Stunnenberg H, Sun J, van de Veerdonk FL, Weis S, Williams DL, Xavier R, Netea MG (2021) Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat Immunol 22(1), 2-6.

Mourits VP, van Puffelen JH, Novakovic B, Bruno M, Ferreira AV, Arts RJ, Groh L, Crișan TO, Zwaag J, Jentho E, Kox M, Pickkers P, van de Veerdonk FL, Weis S, Oosterwijk E, Vermeulen SH, Netea MG, Joosten LA (2021) Lysine methyltransferase G9a is an important modulator of trained immunity. Clin Transl Immunol 10(2), e1253.

Bauer M, Weis S, Netea MG, Wetzker R (2018) Remembering pathogen dose: Long-term adaptation in innate immunity. Trends Immunol 39(6), 438-45.

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 USA 118(42).

Jentho E, Weis S (2021) DAMPs and innate immune training. Front Immunol, accepted.

Staff

Joel Guerra
Lea Hauswald
Emma King