000132779 001__ 132779
000132779 005__ 20240315113107.0
000132779 0247_ $$2doi$$a10.1016/j.isci.2024.108869
000132779 0248_ $$2sideral$$a137697
000132779 037__ $$aART-2024-137697
000132779 041__ $$aeng
000132779 100__ $$aMinute, Luna
000132779 245__ $$aHeat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally
000132779 260__ $$c2024
000132779 5060_ $$aAccess copy available to the general public$$fUnrestricted
000132779 5203_ $$aTrained 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.
000132779 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000132779 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000132779 700__ $$aBergón-Gutiérrez, Marta
000132779 700__ $$aMata-Martínez, Pablo
000132779 700__ $$aFernández-Pascual, Jaime
000132779 700__ $$aTerrón, Verónica
000132779 700__ $$aBravo-Robles, Laura
000132779 700__ $$aBiçakcioglu, Gülce
000132779 700__ $$aZapata-Fernández, Gabriela
000132779 700__ $$0(orcid)0000-0001-7897-9173$$aAguiló, Nacho$$uUniversidad de Zaragoza
000132779 700__ $$aLópez-Collazo, Eduardo
000132779 700__ $$adel Fresno, Carlos
000132779 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000132779 773__ $$g27, 2 (2024), 108869 [16 pp.]$$piScience$$tISCIENCE$$x2589-0042
000132779 8564_ $$s3416554$$uhttps://zaguan.unizar.es/record/132779/files/texto_completo.pdf$$yVersión publicada
000132779 8564_ $$s1173814$$uhttps://zaguan.unizar.es/record/132779/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000132779 909CO $$ooai:zaguan.unizar.es:132779$$particulos$$pdriver
000132779 951__ $$a2024-03-15-08:49:24
000132779 980__ $$aARTICLE