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References
Divangahi, M. et al. Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat. Immunol. 22, 2–6 (2021).
Luna, E., Bruce, T. J., Roberts, M. R., Flors, V. & Ton, J. Next-generation systemic acquired resistance. Plant Physiol. 158, 844–853 (2012).
Kurtz, J. & Franz, K. Innate defence: evidence for memory in invertebrate immunity. Nature 425, 37–38 (2003).
Slaughter, A. et al. Descendants of primed Arabidopsis plants exhibit resistance to biotic stress. Plant Physiol. 158, 835–843 (2012).
Stensballe, L. G. et al. BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial. Arch. Dis. Child. 102, 224–231 (2017).
Mawa, P. A. et al. Maternal BCG scar is associated with increased infant proinflammatory immune responses. Vaccine 35, 273–282 (2017).
Freyne, B. et al. Neonatal BCG vaccination influences cytokine responses to Toll-like receptor ligands and heterologous antigens. J. Infect. Dis. 217, 1798–1808 (2018).
Katzmarski, N. et al. Transmission of trained immunity and heterologous resistance to infections across generations. Nat. Immunol. 22, 1382–1390 (2021).
Kaufmann, E. et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190.e119 (2018).
Adler, I. D. Comparison of the duration of spermatogenesis between male rodents and humans. Mutat. Res. 352, 169–172 (1996).
Stewart, K. R., Veselovska, L. & Kelsey, G. Establishment and functions of DNA methylation in the germline. Epigenomics 8, 1399–1413 (2016).
Tang, W. W. et al. A unique gene regulatory network resets the human germline epigenome for development. Cell 161, 1453–1467 (2015).
Radford, E. J. et al. In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science 345, 1255903 (2014).
Carone, B. R. et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143, 1084–1096 (2010).
Zhang, Y. et al. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nat. Cell Biol. 20, 535–540 (2018).
Radford, E. J. Exploring the extent and scope of epigenetic inheritance. Nat. Rev. Endocrinol. 14, 345–355 (2018).
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E.K., M.L., J.D., J.C., S.T.N. and K.T. performed experiments and analyzed data. E.K., D.C.V., L.B.B. and M.D. designed experiments and discussed results and strategy. E.K., L.B.B. and M.D. wrote the manuscript.
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Extended data
Extended Data Fig. 1 Antibiotic treatment of BCG i.v.–vaccinated mice does not unmask intergenerational resistance.
a, Mice were iv-vaccinated with BCG-Tice (1 × 106 CFU). After one-month BCG vaccination, to eliminate live BCG, mice were treated with Antibiotics (INH + Rifampicin) for 4wks, followed by a 2wks wash-out period. Subsequently, naïve or BCG-vaccinated mice were mated and the adult offspring were infected with M. tuberculosis (~50 CFU, H37Rv aerosol, male offspring) or IAV sublethal (50PFU) or lethal (90PFU) dose (intranasally; female offspring). b, Lung and spleen CFU at 4wks post Mtb infection. c, Lung PFU 3d post sublethal IAV infection. d, F1.2 and F1.3 offspring from BCG-vaccinated and unvaccinated mice were treated with the antibitics and then were infected with Mtb or IAV. e, Survival after lethal IAV infection in F1.2 and F1.3. F1.2 (f) and F1.3 (g) Lung and spleen CFU 4wks post Mtb infection. All CFU data are displayed in log scale. There was no statistically significant difference between groups.
Extended Data Fig. 2 BCG vaccination in the offspring of vaccinated parents does not enhance trained immunity in macrophages.
a, Mice were vaccinated with BCG-iv (1 × 106 CFU) for one month and mated with vaccinated or naive counterparts. 6–8 week-old F1.1 and F1.3 offspring were then vaccinated or not with BCG-iv (1 × 106 CFU). b,c, At 1 month post BCG vaccination, protective capacities of BMDM from BCG-iv vaccinated and nonvaccinated F1.1 (b), or F1.3 (c) offspring from naïve or BCG-iv vaccinated parents were assessed against M. tuberculosis (H37Rv, MOI 1) infection. * p < 0.05.
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Kaufmann, E., Landekic, M., Downey, J. et al. Lack of evidence for intergenerational inheritance of immune resistance to infections. Nat Immunol 23, 203–207 (2022). https://doi.org/10.1038/s41590-021-01102-0
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DOI: https://doi.org/10.1038/s41590-021-01102-0
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