BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment.
Cell Host Microbe
; 28(2): 322-334.e5, 2020 08 12.
Article
en En
| MEDLINE
| ID: mdl-32544459
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Células Madre Hematopoyéticas
/
Vacuna BCG
/
Monocitos
/
Granulocitos
/
Hematopoyesis
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cell Host Microbe
Asunto de la revista:
MICROBIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania