Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer.
The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens...
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2014-10-01
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doaj-1f267804eb5843b3ae7bd69978fd754d2020-11-24T21:46:28ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-10-011010e100448510.1371/journal.ppat.1004485Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer.Kathrin BuffenMarije OostingJessica QuintinAylwin NgJohanneke KleinnijenhuisVinod KumarEsther van de VosseCisca WijmengaReinout van CrevelEgbert OosterwijkAnne J GrotenhuisSita H VermeulenLambertus A KiemeneyFrank L van de VeerdonkGeorgios ChamilosRamnik J XavierJos W M van der MeerMihai G NeteaLeo A B JoostenThe anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as β-glucans or BCG. Single nucleotide polymorphisms (SNPs) in the autophagy genes ATG2B (rs3759601) and ATG5 (rs2245214) influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG.http://europepmc.org/articles/PMC4214925?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kathrin Buffen Marije Oosting Jessica Quintin Aylwin Ng Johanneke Kleinnijenhuis Vinod Kumar Esther van de Vosse Cisca Wijmenga Reinout van Crevel Egbert Oosterwijk Anne J Grotenhuis Sita H Vermeulen Lambertus A Kiemeney Frank L van de Veerdonk Georgios Chamilos Ramnik J Xavier Jos W M van der Meer Mihai G Netea Leo A B Joosten |
spellingShingle |
Kathrin Buffen Marije Oosting Jessica Quintin Aylwin Ng Johanneke Kleinnijenhuis Vinod Kumar Esther van de Vosse Cisca Wijmenga Reinout van Crevel Egbert Oosterwijk Anne J Grotenhuis Sita H Vermeulen Lambertus A Kiemeney Frank L van de Veerdonk Georgios Chamilos Ramnik J Xavier Jos W M van der Meer Mihai G Netea Leo A B Joosten Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. PLoS Pathogens |
author_facet |
Kathrin Buffen Marije Oosting Jessica Quintin Aylwin Ng Johanneke Kleinnijenhuis Vinod Kumar Esther van de Vosse Cisca Wijmenga Reinout van Crevel Egbert Oosterwijk Anne J Grotenhuis Sita H Vermeulen Lambertus A Kiemeney Frank L van de Veerdonk Georgios Chamilos Ramnik J Xavier Jos W M van der Meer Mihai G Netea Leo A B Joosten |
author_sort |
Kathrin Buffen |
title |
Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. |
title_short |
Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. |
title_full |
Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. |
title_fullStr |
Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. |
title_full_unstemmed |
Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. |
title_sort |
autophagy controls bcg-induced trained immunity and the response to intravesical bcg therapy for bladder cancer. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2014-10-01 |
description |
The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as β-glucans or BCG. Single nucleotide polymorphisms (SNPs) in the autophagy genes ATG2B (rs3759601) and ATG5 (rs2245214) influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG. |
url |
http://europepmc.org/articles/PMC4214925?pdf=render |
work_keys_str_mv |
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