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

Tarancón, Raquel (Universidad de Zaragoza) ; Domínguez-Andrés, Jorge ; Uranga, Santiago (Universidad de Zaragoza) ; Ferreira, Anaísa V. ; Groh, Laszlo A. ; Domenech, Mirian ; González-Camacho, Fernando ; Riksen, Niels P. ; Aguilo, Nacho (Universidad de Zaragoza) ; Yuste, José ; Martín, Carlos (Universidad de Zaragoza) ; Netea, Mihai G.

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.

Idioma: Inglés

DOI: 10.1371/journal.ppat.1008404

Año: 2020

Publicado en: PLoS Pathogens 16, 4 (2020), e1008404 [18 pp.]
ISSN: 1553-7366

Factor impacto JCR: 6.823 (2020)

Categ. JCR: MICROBIOLOGY rank: 20 / 136 = 0.147 (2020) - Q1 - T1
Categ. JCR: VIROLOGY rank: 7 / 36 = 0.194 (2020) - Q1 - T1
Categ. JCR: PARASITOLOGY rank: 3 / 38 = 0.079 (2020) - Q1 - T1

Factor impacto SCIMAGO: 3.718 - Genetics (Q1) - Immunology (Q1) - Virology (Q1) - Molecular Biology (Q1) - Parasitology (Q1) - Microbiology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097625-B-100

Tipo y forma: Article (Published version)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Ped.Radio.Sal.Pú.)