1. Transmission of trained immunity and heterologous resistance to infections across generations
- Author
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Gilles Gasparoni, Andreas Schlitzer, Branko Cirovic, Joachim L. Schultze, Didier Le Roy, Kristian Händler, Evangelos J. Giamarellos-Bourboulis, Jorge Domínguez-Andrés, Jörn Walter, Leo A. B. Joosten, Marc Beyer, Jos W. M. van der Meer, Kathrin Kattler, Heidi Theis, Natalie Katzmarski, Mihai G. Netea, Eleonora Ciarlo, Georgios Renieris, Konstantin Lepikhov, and Thierry Roger
- Subjects
Male ,Heredity ,Transcription, Genetic ,genetics [Escherichia coli Infections] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,immunology [Escherichia coli] ,Epigenesis, Genetic ,microbiology [Listeriosis] ,Candida albicans ,Immunology and Allergy ,Listeriosis ,Myeloid Cells ,genetics [Listeriosis] ,Escherichia coli Infections ,Cells, Cultured ,immunology [Escherichia coli Infections] ,metabolism [Spermatozoa] ,biology ,immunology [Listeriosis] ,Effector ,Candidiasis ,immunology [Listeria monocytogenes] ,Spermatozoa ,pathogenicity [Candida albicans] ,metabolism [Escherichia coli Infections] ,immunology [Candidiasis] ,pathogenicity [Escherichia coli] ,immunology [Candida albicans] ,DNA methylation ,Host-Pathogen Interactions ,Transgene ,genetics [Candidiasis] ,Immunology ,Heterologous ,Mice, Transgenic ,metabolism [Myeloid Cells] ,Immune system ,Immunity ,Escherichia coli ,Animals ,Epigenetics ,ddc:610 ,metabolism [Listeriosis] ,pathogenicity [Listeria monocytogenes] ,microbiology [Escherichia coli Infections] ,microbiology [Candidiasis] ,DNA Methylation ,biology.organism_classification ,Listeria monocytogenes ,Immunity, Innate ,genetics [Immunity, Innate] ,Disease Models, Animal ,microbiology [Myeloid Cells] ,metabolism [Candidiasis] ,immunology [Spermatozoa] ,immunology [Myeloid Cells] - Abstract
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. Transgenerational transmission of acquired immunological traits has been demonstrated in invertebrates and plants but not mammals. Katzmarski et al. demonstrate that trained immunity that protects against heterologous infections can be transmitted to F2 offspring.
- Published
- 2021
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