Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity
- 16 June 2015
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 98 (6), 995-1001
- https://doi.org/10.1189/jlb.4ma0215-059r
Abstract
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.Keywords
Funding Information
- Scientific Research
- ERC starting (ERC-StG-310372)
- Netherlands Organization for Scientific Research
- C.S.B.
- ERC starting (ERC-StG-243149)
- P.A.
- Danish International Development Agency (DNRF108)
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