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oai:repisalud.isciii.es:20.500.12105/94492024-11-29T09:17:29Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16973

00925njm 22002777a 4500 dc Tarancón, Raquel author Domínguez-Andrés, Jorge author Uranga, Santiago author Ferreira, Anaísa V author Groh, Laszlo A author Domenech Lucas, Mirian author Gonzalez-Camacho, Fernando author Riksen, Niels P author Aguilo, Nacho author Yuste, Jose Enrique author Martín, Carlos author Netea, Mihai G author 2020-04 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. PLoS Pathog. 2020 Apr 2;16(4):e1008404 10.1371/journal.ppat.1008404 1553-7374 1553-7374 PLoS pathogens 32240273 http://hdl.handle.net/20.500.12105/9449 New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia