BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

Rob J W Arts, Simone J C F M Moorlag, Boris Novakovic, Yang Li, Shuang-Yin Wang, Marije Oosting, Vinod Kumar, Ramnik J Xavier, Cisca Wijmenga, Leo A B Joosten, Chantal B E M Reusken, Christine S Benn, Peter Aaby, Marion P Koopmans, Hendrik G Stunnenberg, Reinout van Crevel, Mihai G Netea

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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. In this paper, Arts et al. describe that BCG vaccination induces genome-wide epigenetic reprogramming of human monocytes that correlates with protection against experimental viral infection. Reduction of viremia correlated with upregulation of non-specific IL-1β production, and genetic polymorphisms in the IL-1 pathway affect the induction of trained immunity by BCG.

OriginalsprogEngelsk
TidsskriftCell Host & Microbe
Vol/bind23
Udgave nummer1
Sider (fra-til)89-100.e5
ISSN1931-3128
DOI
StatusUdgivet - 10. jan. 2018

Fingeraftryk

Virus Diseases
Epigenomics
Up-Regulation
Yellow Fever Vaccine
Yellow fever virus
Attenuated Vaccines
Genetic Polymorphisms
Placebos

Citer dette

Arts, R. J. W., Moorlag, S. J. C. F. M., Novakovic, B., Li, Y., Wang, S-Y., Oosting, M., ... Netea, M. G. (2018). BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host & Microbe, 23(1), 89-100.e5. https://doi.org/10.1016/j.chom.2017.12.010
Arts, Rob J W ; Moorlag, Simone J C F M ; Novakovic, Boris ; Li, Yang ; Wang, Shuang-Yin ; Oosting, Marije ; Kumar, Vinod ; Xavier, Ramnik J ; Wijmenga, Cisca ; Joosten, Leo A B ; Reusken, Chantal B E M ; Benn, Christine S ; Aaby, Peter ; Koopmans, Marion P ; Stunnenberg, Hendrik G ; van Crevel, Reinout ; Netea, Mihai G. / BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. I: Cell Host & Microbe. 2018 ; Bind 23, Nr. 1. s. 89-100.e5.
@article{266e47383f894a60bfdfd44c0bc5519a,
title = "BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity",
abstract = "The tuberculosis vaccine bacillus Calmette-Gu{\'e}rin (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. In this paper, Arts et al. describe that BCG vaccination induces genome-wide epigenetic reprogramming of human monocytes that correlates with protection against experimental viral infection. Reduction of viremia correlated with upregulation of non-specific IL-1β production, and genetic polymorphisms in the IL-1 pathway affect the induction of trained immunity by BCG.",
keywords = "BCG, IL-1, epigenetics, innate immune memory, monocytes, non-specific effects of vaccines, trained immunity, yellow fever vaccine",
author = "Arts, {Rob J W} and Moorlag, {Simone J C F M} and Boris Novakovic and Yang Li and Shuang-Yin Wang and Marije Oosting and Vinod Kumar and Xavier, {Ramnik J} and Cisca Wijmenga and Joosten, {Leo A B} and Reusken, {Chantal B E M} and Benn, {Christine S} and Peter Aaby and Koopmans, {Marion P} and Stunnenberg, {Hendrik G} and {van Crevel}, Reinout and Netea, {Mihai G}",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2018",
month = "1",
day = "10",
doi = "10.1016/j.chom.2017.12.010",
language = "English",
volume = "23",
pages = "89--100.e5",
journal = "Cell Host & Microbe",
issn = "1931-3128",
publisher = "Cell Press",
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Arts, RJW, Moorlag, SJCFM, Novakovic, B, Li, Y, Wang, S-Y, Oosting, M, Kumar, V, Xavier, RJ, Wijmenga, C, Joosten, LAB, Reusken, CBEM, Benn, CS, Aaby, P, Koopmans, MP, Stunnenberg, HG, van Crevel, R & Netea, MG 2018, 'BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity', Cell Host & Microbe, bind 23, nr. 1, s. 89-100.e5. https://doi.org/10.1016/j.chom.2017.12.010

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. / Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris; Li, Yang; Wang, Shuang-Yin; Oosting, Marije; Kumar, Vinod; Xavier, Ramnik J; Wijmenga, Cisca; Joosten, Leo A B; Reusken, Chantal B E M; Benn, Christine S; Aaby, Peter; Koopmans, Marion P; Stunnenberg, Hendrik G; van Crevel, Reinout; Netea, Mihai G.

I: Cell Host & Microbe, Bind 23, Nr. 1, 10.01.2018, s. 89-100.e5.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

AU - Arts, Rob J W

AU - Moorlag, Simone J C F M

AU - Novakovic, Boris

AU - Li, Yang

AU - Wang, Shuang-Yin

AU - Oosting, Marije

AU - Kumar, Vinod

AU - Xavier, Ramnik J

AU - Wijmenga, Cisca

AU - Joosten, Leo A B

AU - Reusken, Chantal B E M

AU - Benn, Christine S

AU - Aaby, Peter

AU - Koopmans, Marion P

AU - Stunnenberg, Hendrik G

AU - van Crevel, Reinout

AU - Netea, Mihai G

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2018/1/10

Y1 - 2018/1/10

N2 - 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. In this paper, Arts et al. describe that BCG vaccination induces genome-wide epigenetic reprogramming of human monocytes that correlates with protection against experimental viral infection. Reduction of viremia correlated with upregulation of non-specific IL-1β production, and genetic polymorphisms in the IL-1 pathway affect the induction of trained immunity by BCG.

AB - 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. In this paper, Arts et al. describe that BCG vaccination induces genome-wide epigenetic reprogramming of human monocytes that correlates with protection against experimental viral infection. Reduction of viremia correlated with upregulation of non-specific IL-1β production, and genetic polymorphisms in the IL-1 pathway affect the induction of trained immunity by BCG.

KW - BCG

KW - IL-1

KW - epigenetics

KW - innate immune memory

KW - monocytes

KW - non-specific effects of vaccines

KW - trained immunity

KW - yellow fever vaccine

U2 - 10.1016/j.chom.2017.12.010

DO - 10.1016/j.chom.2017.12.010

M3 - Journal article

C2 - 29324233

VL - 23

SP - 89-100.e5

JO - Cell Host & Microbe

JF - Cell Host & Microbe

SN - 1931-3128

IS - 1

ER -