132779 20260217205448.0 doi 10.1016/j.isci.2024.108869 sideral 137697 ART-2024-137697 eng Minute, Luna Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally 2024 Access copy available to the general public Unrestricted 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. info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 4.1 2024 MULTIDISCIPLINARY SCIENCES 22 / 136 = 0.162 2024 Q1 T1 1.363 2024 Multidisciplinary 2024 Q1 6.9 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Bergón-Gutiérrez, Marta Mata-Martínez, Pablo Fernández-Pascual, Jaime Terrón, Verónica Bravo-Robles, Laura Biçakcioglu, Gülce Zapata-Fernández, Gabriela Aguiló, Nacho Universidad de Zaragoza (orcid)0000-0001-7897-9173 López-Collazo, Eduardo del Fresno, Carlos 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 27, 2 (2024), 108869 [16 pp.] iScience ISCIENCE 2589-0042 3416554 http://zaguan.unizar.es/record/132779/files/texto_completo.pdf Versión publicada 1173814 http://zaguan.unizar.es/record/132779/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:132779 articulos driver 2026-02-17-20:18:20 ARTICLE