Transmission of trained immunity and heterologous resistance to infections across generations

• Published in: Nature immunology Vol. 22; no. 11; pp. 1382 - 1390
• Main Authors: Katzmarski, Natalie, Domínguez-Andrés, Jorge, Cirovic, Branko, Renieris, Georgios, Ciarlo, Eleonora, Le Roy, Didier, Lepikhov, Konstantin, Kattler, Kathrin, Gasparoni, Gilles, Händler, Kristian, Theis, Heidi, Beyer, Marc, van der Meer, Jos W M, Joosten, Leo A B, Walter, Jörn, Schultze, Joachim L, Roger, Thierry, Giamarellos-Bourboulis, Evangelos J, Schlitzer, Andreas, Netea, Mihai G
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2021
• Subjects: Animals; Bone marrow; Candida albicans; Candida albicans - immunology; Candida albicans - pathogenicity; Candidiasis - genetics; Candidiasis - immunology; Candidiasis - metabolism; Candidiasis - microbiology; Cells, Cultured; Deoxyribonucleic acid; Disease Models, Animal; Disseminated infection; DNA; DNA Methylation; E coli; Endotoxins; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Escherichia coli; Escherichia coli - immunology; Escherichia coli - pathogenicity; Escherichia coli Infections - genetics; Escherichia coli Infections - immunology; Escherichia coli Infections - metabolism; Escherichia coli Infections - microbiology; Genetic aspects; Health aspects; Heredity; Host-Pathogen Interactions; Immunity; Immunity, Innate - genetics; Immunological research; Infections; Intergenerational transmission; Invertebrates; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeria monocytogenes - pathogenicity; Listeriosis - genetics; Listeriosis - immunology; Listeriosis - metabolism; Listeriosis - microbiology; Male; Mammals; Mice, Transgenic; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Cells - microbiology; Offspring; Physiological aspects; Progenitor cells; Spermatozoa - immunology; Spermatozoa - metabolism; Stem cells; Transcription; Transcription, Genetic; Germany
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/s41590-021-01052-7

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.