Cell host & microbe · 2020
BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Cirovic Branko, de Bree L Charlotte J, Groh Laszlo, Blok Bas A, Chan Joyce, van der Velden Walter J F M, Bremmers M E J, van Crevel Reinout, Händler Kristian, Picelli Simone, Schulte-Schrepping Jonas, Klee Kathrin, Oosting Marije, Koeken Valerie A C M, van Ingen Jakko, Li Yang, Benn Christine S, Schultze Joachim L, Joosten Leo A B, Curtis Nigel, Netea Mihai G, Schlitzer Andreas
Аннотация
Induction of trained immunity by Bacille-Calmette-Guérin (BCG) vaccination mediates beneficial heterologous effects, but the mechanisms underlying its persistence and magnitude remain elusive. In this study, we show that BCG vaccination in healthy human volunteers induces a persistent transcriptional program connected to myeloid cell development and function within the hematopoietic stem and progenitor cell (HSPC) compartment in the bone marrow. We identify hepatic nuclear factor (HNF) family members 1a and b as crucial regulators of this transcriptional shift. These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1 SNP variants that correlate with trained immunity, and elevated serum concentrations of the HNF1 target alpha-1 antitrypsin. Additionally, transcriptomic HSPC remodeling was epigenetically conveyed to peripheral CD14+ monocytes, displaying an activated transcriptional signature three months after BCG vaccination. Taken together, transcriptomic, epigenomic, and functional reprogramming of HSPCs and peripheral monocytes is a hallmark of BCG-induced trained immunity in humans.
Предметные рубрики MeSH
BCG VaccineBone MarrowBone Marrow CellsCytokinesFemaleGranulocytesHealthy VolunteersHematopoiesisHematopoietic Stem CellsHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHumansLipopolysaccharide ReceptorsMaleMonocytesMycobacterium bovisTranscription, GeneticTranscriptomeVaccinationYoung Adultalpha 1-Antitrypsin