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New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia

Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects of Bacillus Calmette-Guerin (BCG), the current vaccine against tuberculosis, have been related not only to specific induction o...

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Autores principales: Tarancón, Raquel, Domínguez-Andrés, Jorge, Uranga, Santiago, Ferreira, Anaísa V., Groh, Laszlo A., Domenech, Mirian, González-Camacho, Fernando, Riksen, Niels P., Aguilo, Nacho, Yuste, José, Martín, Carlos, Netea, Mihai G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117655/
https://www.ncbi.nlm.nih.gov/pubmed/32240273
http://dx.doi.org/10.1371/journal.ppat.1008404
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author Tarancón, Raquel
Domínguez-Andrés, Jorge
Uranga, Santiago
Ferreira, Anaísa V.
Groh, Laszlo A.
Domenech, Mirian
González-Camacho, Fernando
Riksen, Niels P.
Aguilo, Nacho
Yuste, José
Martín, Carlos
Netea, Mihai G.
author_facet Tarancón, Raquel
Domínguez-Andrés, Jorge
Uranga, Santiago
Ferreira, Anaísa V.
Groh, Laszlo A.
Domenech, Mirian
González-Camacho, Fernando
Riksen, Niels P.
Aguilo, Nacho
Yuste, José
Martín, Carlos
Netea, Mihai G.
author_sort Tarancón, Raquel
collection PubMed
description Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects of Bacillus Calmette-Guerin (BCG), the current vaccine against tuberculosis, have been related not only to specific induction of T-cell immunity, but also with the long-term epigenetic and metabolic reprogramming of the cells from the innate immune system through a process termed trained immunity. Here we show that MTBVAC, a live attenuated strain of Mycobacterium tuberculosis, safe and immunogenic against tuberculosis antigens in adults and newborns, is also able to generate trained immunity through the induction of glycolysis and glutaminolysis and the accumulation of histone methylation marks at the promoters of proinflammatory genes, facilitating an enhanced response after secondary challenge with non-related bacterial stimuli. Importantly, these findings in human primary myeloid cells are complemented by a strong MTBVAC-induced heterologous protection against a lethal challenge with Streptococcus pneumoniae in an experimental murine model of pneumonia.
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spelling pubmed-71176552020-04-09 New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia Tarancón, Raquel Domínguez-Andrés, Jorge Uranga, Santiago Ferreira, Anaísa V. Groh, Laszlo A. Domenech, Mirian González-Camacho, Fernando Riksen, Niels P. Aguilo, Nacho Yuste, José Martín, Carlos Netea, Mihai G. PLoS Pathog Research Article Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects of Bacillus Calmette-Guerin (BCG), the current vaccine against tuberculosis, have been related not only to specific induction of T-cell immunity, but also with the long-term epigenetic and metabolic reprogramming of the cells from the innate immune system through a process termed trained immunity. Here we show that MTBVAC, a live attenuated strain of Mycobacterium tuberculosis, safe and immunogenic against tuberculosis antigens in adults and newborns, is also able to generate trained immunity through the induction of glycolysis and glutaminolysis and the accumulation of histone methylation marks at the promoters of proinflammatory genes, facilitating an enhanced response after secondary challenge with non-related bacterial stimuli. Importantly, these findings in human primary myeloid cells are complemented by a strong MTBVAC-induced heterologous protection against a lethal challenge with Streptococcus pneumoniae in an experimental murine model of pneumonia. Public Library of Science 2020-04-02 /pmc/articles/PMC7117655/ /pubmed/32240273 http://dx.doi.org/10.1371/journal.ppat.1008404 Text en © 2020 Tarancón et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tarancón, Raquel
Domínguez-Andrés, Jorge
Uranga, Santiago
Ferreira, Anaísa V.
Groh, Laszlo A.
Domenech, Mirian
González-Camacho, Fernando
Riksen, Niels P.
Aguilo, Nacho
Yuste, José
Martín, Carlos
Netea, Mihai G.
New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
title New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
title_full New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
title_fullStr New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
title_full_unstemmed New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
title_short New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
title_sort new live attenuated tuberculosis vaccine mtbvac induces trained immunity and confers protection against experimental lethal pneumonia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117655/
https://www.ncbi.nlm.nih.gov/pubmed/32240273
http://dx.doi.org/10.1371/journal.ppat.1008404
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