TY  - JOUR
AU  - Katzmarski, Natalie
AU  - Domínguez-Andrés, Jorge
AU  - Cirovic, Branko
AU  - Renieris, Georgios
AU  - Ciarlo, Eleonora
AU  - Le Roy, Didier
AU  - Lepikhov, Konstantin
AU  - Kattler, Kathrin
AU  - Gasparoni, Gilles
AU  - Händler, Kristian
AU  - Theis, Heidi
AU  - Beyer, Marc
AU  - van der Meer, Jos W M
AU  - Joosten, Leo A B
AU  - Walter, Jörn
AU  - Schultze, Joachim L
AU  - Roger, Thierry
AU  - Giamarellos-Bourboulis, Evangelos J
AU  - Schlitzer, Andreas
AU  - Netea, Mihai G
TI  - Transmission of trained immunity and heterologous resistance to infections across generations.
JO  - Nature immunology
VL  - 22
IS  - 11
SN  - 1529-2916
CY  - London
PB  - Springer Nature Limited
M1  - DZNE-2021-01539
SP  - 1382 - 1390
PY  - 2021
AB  - Intergenerational inheritance of immune traits linked to epigenetic modifications has been demonstrated in plants and invertebrates. Here we provide evidence for transmission of trained immunity across generations to murine progeny that survived a sublethal systemic infection with Candida albicans or a zymosan challenge. The progeny of trained mice exhibited cellular, developmental, transcriptional and epigenetic changes associated with the bone marrow-resident myeloid effector and progenitor cell compartment. Moreover, the progeny of trained mice showed enhanced responsiveness to endotoxin challenge, alongside improved protection against systemic heterologous Escherichia coli and Listeria monocytogenes infections. Sperm DNA of parental male mice intravenously infected with the fungus C. albicans showed DNA methylation differences linked to immune gene loci. These results provide evidence for inheritance of trained immunity in mammals, enhancing protection against infections.
KW  - Animals
KW  - Candida albicans: immunology
KW  - Candida albicans: pathogenicity
KW  - Candidiasis: genetics
KW  - Candidiasis: immunology
KW  - Candidiasis: metabolism
KW  - Candidiasis: microbiology
KW  - Cells, Cultured
KW  - DNA Methylation
KW  - Disease Models, Animal
KW  - Epigenesis, Genetic
KW  - Escherichia coli: immunology
KW  - Escherichia coli: pathogenicity
KW  - Escherichia coli Infections: genetics
KW  - Escherichia coli Infections: immunology
KW  - Escherichia coli Infections: metabolism
KW  - Escherichia coli Infections: microbiology
KW  - Heredity
KW  - Host-Pathogen Interactions
KW  - Immunity, Innate: genetics
KW  - Listeria monocytogenes: immunology
KW  - Listeria monocytogenes: pathogenicity
KW  - Listeriosis: genetics
KW  - Listeriosis: immunology
KW  - Listeriosis: metabolism
KW  - Listeriosis: microbiology
KW  - Male
KW  - Mice, Transgenic
KW  - Myeloid Cells: immunology
KW  - Myeloid Cells: metabolism
KW  - Myeloid Cells: microbiology
KW  - Spermatozoa: immunology
KW  - Spermatozoa: metabolism
KW  - Transcription, Genetic
LB  - PUB:(DE-HGF)16
C6  - pmid:34663978
DO  - DOI:10.1038/s41590-021-01052-7
UR  - https://pub.dzne.de/record/162884
ER  -