| Literature DB >> 29324233 |
Rob J W Arts1, Simone J C F M Moorlag1, Boris Novakovic2, Yang Li3, Shuang-Yin Wang1, Marije Oosting1, Vinod Kumar3, Ramnik J Xavier4, Cisca Wijmenga3, Leo A B Joosten1, Chantal B E M Reusken5, Christine S Benn6, Peter Aaby6, Marion P Koopmans5, Hendrik G Stunnenberg2, Reinout van Crevel1, Mihai G Netea7.
Abstract
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1β, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNγ response. The importance of IL-1β for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1β as a mediator of trained immunity responses.Entities:
Keywords: BCG; IL-1; epigenetics; innate immune memory; monocytes; non-specific effects of vaccines; trained immunity; yellow fever vaccine
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Year: 2018 PMID： 29324233 DOI： 10.1016/j.chom.2017.12.010
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023