Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/9449
Título
New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia
Autor(es)
Tarancón, Raquel | Domínguez-Andrés, Jorge | Uranga, Santiago | Ferreira, Anaísa V | Groh, Laszlo A | Domenech Lucas, Mirian ISCIII | Gonzalez-Camacho, Fernando ISCIII | Riksen, Niels P | Aguilo, Nacho | Yuste, Jose Enrique ISCIII | Martín, Carlos | Netea, Mihai G
Fecha de publicación
2020-04
Cita
PLoS Pathog. 2020 Apr 2;16(4):e1008404
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Versión en línea
DOI
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