학술논문
Transmission of trained immunity and heterologous resistance to infections across generations
Document Type
Report
Author
Katzmarski, Natalie; Domínguez-Andrés, Jorge; Cirovic, Branko; Renieris, Georgios; Ciarlo, Eleonora; Le Roy, Didier; Lepikhov, Konstantin; Kattler, Kathrin; Gasparoni, Gilles; Handler, Kristian; Theis, Heidi; Beyer, Marc; van der Meer, Jos W.M.; Joosten, Leo A.B.; Walter, Jorn; Schultze, Joachim L.; Roger, Thierry
Source
Nature Immunology. November 2021, Vol. 22 Issue 11, p1382, 9 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Natalie Katzmarski [sup.1] , Jorge Domínguez-Andrés [sup.2] [sup.3] , Branko Cirovic [sup.1] , Georgios Renieris [sup.4] , Eleonora Ciarlo [sup.5] , Didier Le Roy [sup.5] , Konstantin Lepikhov [sup.6] [...]
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.
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.