Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity. Issue 6 (16th June 2015)

• Record Type: Journal Article
• Authors: Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter; Joosten, Leo A B; de Jong, Dirk; van der Meer, Jos W M; Benn, Christine Stabell; van Crevel, Reinout; Netea, Mihai G
• Is Part Of: Journal of leukocyte biology. Volume 98:Issue 6(2015)
• Page Start: 995
• Page End: 1001
• Publication Date: 2015-06-16
• Subjects: trained immunity -- heterologous immunity -- nonspecific vaccination effects; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4MA0215-059R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : γ-irradiated BCG induces heterologous immunity, but nottrained immunity in vivo, in contrast to BCG which induces both. 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.