Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

Rob J W Arts, Bastiaan A Blok, Peter Aaby, Leo A B Joosten, Dirk de Jong, Jos W M van der Meer, Christine Stabell Benn, Reinout van Crevel, Mihai G Netea

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BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity but not in immunocompromised hosts, as it is a live, attenuated vaccine. Therefore, we assessed whether killed γBCG has similar potentiating effects. In an in vitro model of trained immunity, human monocytes were incubated with γBCG for 24 h and restimulated after 6 d. Cytokine production and the role of pattern recognition receptors and histone methylation markers were assessed. The in vivo effects of γBCG vaccination were studied in a proof-of-principle trial in 15 healthy volunteers. γBCG induced trained immunity in vitro via the NOD2 receptor pathway and up-regulation of H3K4me3 histone methylation. However, these effects were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γBCG induces mainly heterologous effects on the adaptive-immune system, whereas effects on innate cytokine production are limited.

TidsskriftJournal of Leukocyte Biology
Udgave nummer6
Sider (fra-til)995-1001
StatusUdgivet - 2015



Arts, R. J. W., Blok, B. A., Aaby, P., Joosten, L. A. B., de Jong, D., van der Meer, J. W. M., Benn, C. S., van Crevel, R., & Netea, M. G. (2015). Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity. Journal of Leukocyte Biology, 98(6), 995-1001. https://doi.org/10.1189/jlb.4MA0215-059R