000097184 001__ 97184
000097184 005__ 20230111103828.0
000097184 0247_ $$2doi$$a10.1016/j.cell.2020.09.062
000097184 0248_ $$2sideral$$a121096
000097184 037__ $$aART-2020-121096
000097184 041__ $$aeng
000097184 100__ $$aKhan, N.
000097184 245__ $$aM. tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity
000097184 260__ $$c2020
000097184 5060_ $$aAccess copy available to the general public$$fUnrestricted
000097184 5203_ $$aA greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium tuberculosis (Mtb). We have shown that systemic administration of Bacille Calmette-Guérin (BCG) or ß-glucan reprograms HSCs in the bone marrow (BM) via a type II interferon (IFN-II) or interleukin-1 (IL1) response, respectively, which confers protective trained immunity against Mtb. Here, we demonstrate that, unlike BCG or ß-glucan, Mtb reprograms HSCs via an IFN-I response that suppresses myelopoiesis and impairs development of protective trained immunity to Mtb. Mechanistically, IFN-I signaling dysregulates iron metabolism, depolarizes mitochondrial membrane potential, and induces cell death specifically in myeloid progenitors. Additionally, activation of the IFN-I/iron axis in HSCs impairs trained immunity to Mtb infection. These results identify an unanticipated immune evasion strategy of Mtb in the BM that controls the magnitude and intrinsic anti-microbial capacity of innate immunity to infection.
000097184 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/LMP117-18$$9info:eu-repo/grantAgreement/EC/FP7/294709/EU/Tissue Damage Control Regulates The Pathogenesis of Immune Mediated Inflammatory Diseases/DAMAGECONTROL$$9info:eu-repo/grantAgreement/EC/H2020/707998/EU/REGULATORY T CELLS AND TISSUE DAMAGE CONTROL/REGDAM$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 707998-REGDAM$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-106859GA-I00$$9info:eu-repo/grantAgreement/ES/MICINN/RYC-2017-23560
000097184 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000097184 590__ $$a41.582$$b2020
000097184 591__ $$aCELL BIOLOGY$$b3 / 195 = 0.015$$c2020$$dQ1$$eT1
000097184 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b2 / 297 = 0.007$$c2020$$dQ1$$eT1
000097184 592__ $$a26.303$$b2020
000097184 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2020$$dQ1
000097184 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000097184 700__ $$aDowney, J.
000097184 700__ $$0(orcid)0000-0002-2980-9685$$aSanz, J.$$uUniversidad de Zaragoza
000097184 700__ $$aKaufmann, E.
000097184 700__ $$aBlankenhaus, B.
000097184 700__ $$aPacis, A.
000097184 700__ $$aPernet, E.
000097184 700__ $$aAhmed, E.
000097184 700__ $$aCardoso, S.
000097184 700__ $$aNijnik, A.
000097184 700__ $$aMazer, B.
000097184 700__ $$aSassetti, C.
000097184 700__ $$aBehr, M.A.
000097184 700__ $$aSoares, M.P.
000097184 700__ $$aBarreiro, L.B.
000097184 700__ $$aDivangahi, M.
000097184 7102_ $$12004$$2405$$aUniversidad de Zaragoza$$bDpto. Física Teórica$$cÁrea Física Teórica
000097184 773__ $$g183, 3 (2020), 752-770.e22$$pCell$$tCELL$$x0092-8674
000097184 8564_ $$s2896619$$uhttps://zaguan.unizar.es/record/97184/files/texto_completo.pdf$$yVersión publicada
000097184 8564_ $$s29517$$uhttps://zaguan.unizar.es/record/97184/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000097184 909CO $$ooai:zaguan.unizar.es:97184$$particulos$$pdriver
000097184 951__ $$a2023-01-11-10:08:09
000097184 980__ $$aARTICLE