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

Felgueres, María-José ; Esteso, Gloria ; García-Jiménez, Álvaro F. ; Benguría, Alberto ; Vázquez, Enrique ; Aguiló, Nacho (Universidad de Zaragoza) ; Puentes, Eugenia ; Dopazo, Ana ; Murillo, Ingrid ; Martín, Carlos (Universidad de Zaragoza) ; Rodríguez, Esteban ; Reyburn, Hugh T. ; Valés-Gómez, Mar

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41541-025-01110-3

Año: 2025

Publicado en: npj Vaccines 10, 1 (2025), 58 [12 pp.]
ISSN: 2059-0105

Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTC-2017-6379-1

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)