Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccine

Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active tuberculosis (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors to control TB, early after infection, the innate immune response must play a r...

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Detalhes bibliográficos
Autores: Felgueres, María José, Esteso, Gloria, García-Jiménez, Álvaro F, Benguría, Alberto, Vázquez, Enrique, Aguiló, Nacho, Puentes, Eugenia, Dopazo, Ana, Murillo, Ingrid, Martín, Carlos, Rodríguez, Esteban, Reyburn, Hugh T, Valés-Gómez, Mar
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/390251
Acesso em linha:http://hdl.handle.net/10261/390251
https://api.elsevier.com/content/abstract/scopus_id/105001115816
Access Level:acceso abierto
Palavra-chave:http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Descrição
Resumo:Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active tuberculosis (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors to control TB, early after infection, the innate immune response must play a role in tackling the disease. Here, we performed in-depth analyses of the acute immune response to MTBVAC, a candidate vaccine engineered from Mtb with the aim of protecting adults from pulmonary TB disease, still a major global challenge. scRNA-seq shows expansion of CD4+ and cytotoxic γδ T-cells, data confirmed by flow cytometry. CD4 T-cells exhibited lower HLA-DR and higher L-selectin expression, compared to BCG-stimulation, indicating differential activation or dynamics. Importantly, MTBVAC-activated γδ T-cells had a unique cytotoxic CD16+GZMB+ phenotype, reminiscent of effector cells found in Mtb positive individuals controlling infection. IFN-γ and TNF-α were released in cultures, while IL-17A/F were almost undetectable.

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