Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally

Minute, Luna ; Bergón-Gutiérrez, Marta ; Mata-Martínez, Pablo ; Fernández-Pascual, Jaime ; Terrón, Verónica ; Bravo-Robles, Laura ; Biçakcioglu, Gülce ; Zapata-Fernández, Gabriela ; Aguiló, Nacho (Universidad de Zaragoza) ; López-Collazo, Eduardo ; del Fresno, Carlos

Resumen: Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal β-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications of harnessing TI against infections and cancer, there is a growing need for new, simple, and easy-to-use TI inducers. Here, we demonstrate that heat-killed Mycobacterium tuberculosis (HKMtb) induces TI both in vitro and in vivo. In human monocytes, this effect represents a truly trained process, as HKMtb confers boosted inflammatory responses against various heterologous challenges, such as lipopolysaccharide (Toll-like receptor [TLR] 4 ligand) and R848 (TLR7/8 ligand). Mechanistically, HKMtb-induced TI relies on epigenetic mechanisms in a Syk/HIF-1α-dependent manner. In vivo, HKMtb induced TI when administered both systemically and intranasally, with the latter generating a more robust TI response. Summarizing, our research has demonstrated that HKMtb has the potential to act as a mucosal immunotherapy that can successfully induce trained responses.

Idioma: Inglés

DOI: 10.1016/j.isci.2024.108869

Año: 2024

Publicado en: ISCIENCE 27, 2 (2024), 108869 [16 pp.]
ISSN: 2589-0042

Tipo y forma: Article (Published version)

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