000160936 001__ 160936
000160936 005__ 20251017144632.0
000160936 0247_ $$2doi$$a10.1016/j.celrep.2025.115657
000160936 0248_ $$2sideral$$a144056
000160936 037__ $$aART-2025-144056
000160936 041__ $$aeng
000160936 100__ $$aMaserumule, Charlotte
000160936 245__ $$aPhagosomal RNA sensing through TLR8 controls susceptibility to tuberculosis
000160936 260__ $$c2025
000160936 5060_ $$aAccess copy available to the general public$$fUnrestricted
000160936 5203_ $$aGenetic determinants of susceptibility to Mycobacterium tuberculosis (Mtb) remain poorly understood but could provide insights into critical pathways involved in infection, informing host-directed therapies and enabling risk stratification at individual and population levels. Through a genome-wide forward genetic screen, we identify Toll-like receptor 8 (TLR8) as a key regulator of intracellular killing of Mtb. Pharmacological TLR8 activation enhances the killing of phylogenetically diverse clinical isolates of drug-susceptible and multidrug-resistant Mtb by macrophages and during in vivo infection in mice. TLR8 is activated by phagosomal mycobacterial RNA released by extracellular membrane vesicles and enhances xenophagy-dependent Mtb killing. We find that the TLR8 variant M1V, common in Far Eastern populations, enhances intracellular killing of Mtb through preferential signal-dependent trafficking to phagosomes. TLR8 signaling may, therefore, both regulate susceptibility to tuberculosis and provide novel drug targets.
000160936 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-110240RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-136611OB-I00
000160936 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000160936 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000160936 700__ $$aPassemar, Charlotte
000160936 700__ $$aOh, Olivia S.H.
000160936 700__ $$aHegyi, Kriztina
000160936 700__ $$aBrown, Karen
000160936 700__ $$aWeimann, Aaron
000160936 700__ $$aDinan, Adam
000160936 700__ $$aDavila, Sonia
000160936 700__ $$aKlapholz, Catherine
000160936 700__ $$aBryant, Josephine
000160936 700__ $$aVerma, Deepshikha
000160936 700__ $$aGadwa, Jacob
000160936 700__ $$aKrishnananthasivam, Shivankari
000160936 700__ $$aVongtongsalee, Kridakorn
000160936 700__ $$aKendall, Edward
000160936 700__ $$aTrelles, Andres
000160936 700__ $$aHibberd, Martin L.
000160936 700__ $$0(orcid)0000-0002-2980-9685$$aSanz, Joaquín$$uUniversidad de Zaragoza
000160936 700__ $$aBertol, Jorge
000160936 700__ $$aVázquez-Iniesta, Lucia
000160936 700__ $$aAndi, Kaliappan
000160936 700__ $$aKumar, S. Siva
000160936 700__ $$aOrdway, Diane
000160936 700__ $$aPrados-Rosales, Rafael
000160936 700__ $$aMacAry, Paul A.
000160936 700__ $$aFloto, R. Andres
000160936 7102_ $$12004$$2405$$aUniversidad de Zaragoza$$bDpto. Física Teórica$$cÁrea Física Teórica
000160936 773__ $$g44, 5 (2025), 115657 [21 pp.]$$pCell Reports$$tCell Reports$$x2211-1247
000160936 8564_ $$s5177665$$uhttps://zaguan.unizar.es/record/160936/files/texto_completo.pdf$$yVersión publicada
000160936 8564_ $$s1297967$$uhttps://zaguan.unizar.es/record/160936/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000160936 909CO $$ooai:zaguan.unizar.es:160936$$particulos$$pdriver
000160936 951__ $$a2025-10-17-14:26:47
000160936 980__ $$aARTICLE