000144802 001__ 144802
000144802 005__ 20240906111329.0
000144802 0247_ $$2doi$$a10.1016/j.mucimm.2024.08.006
000144802 0248_ $$2sideral$$a139589
000144802 037__ $$aART-2024-139589
000144802 041__ $$aeng
000144802 100__ $$aChawla, Amanpreet Singh
000144802 245__ $$aDistinct cell death pathways induced by granzymes collectively protect against intestinal Salmonella infection
000144802 260__ $$c2024
000144802 5060_ $$aAccess copy available to the general public$$fUnrestricted
000144802 5203_ $$aIntestinal intraepithelial T lymphocytes (IEL) constitutively express high amounts of the cytotoxic proteases Granzymes (Gzm) A and B and are therefore thought to protect the intestinal epithelium against infection by killing infected epithelial cells. However, the role of IEL granzymes in a protective immune response has yet to be demonstrated. We show that GzmA and GzmB are required to protect mice against oral, but not intravenous, infection with Salmonella enterica serovar Typhimurium, consistent with an intestine-specific role. IEL-intrinsic granzymes mediate the protective effects by controlling intracellular bacterial growth and aiding in cell-intrinsic pyroptotic cell death of epithelial cells. Surprisingly, we found that both granzymes play non-redundant roles. GzmB-/- mice carried significantly lower burdens of Salmonella, as predominant GzmA-mediated cell death effectively reduced bacterial translocation across the intestinal barrier. Conversely, in GzmA-/- mice, GzmB-driven apoptosis favored luminal Salmonella growth by providing nutrients, while still reducing translocation across the epithelial barrier. Together, the concerted actions of both GzmA and GzmB balance cell death mechanisms at the intestinal epithelium to provide optimal control that Salmonella cannot subvert.
000144802 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2020-113963RB-I00$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/B29-17R$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2017-83120-C2-1-R
000144802 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000144802 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000144802 700__ $$aVandereyken, Maud
000144802 700__ $$0(orcid)0000-0002-9730-2210$$aArias, Maykel
000144802 700__ $$0(orcid)0000-0002-1861-5981$$aSantiago, Llipsy
000144802 700__ $$aDikovskaya, Dina
000144802 700__ $$aNguyen, Chi
000144802 700__ $$aSkariah, Neema
000144802 700__ $$aWenner, Nicolas
000144802 700__ $$aGolovchenko, Natasha B.
000144802 700__ $$aThomson, Sarah J.
000144802 700__ $$aOndari, Edna
000144802 700__ $$0(orcid)0000-0001-6778-0636$$aGarzón-Tituaña, Marcela
000144802 700__ $$aAnderson, Christopher J.
000144802 700__ $$aBergkessel, Megan
000144802 700__ $$aC. D. Hinton, Jay
000144802 700__ $$aEdelblum, Karen L.
000144802 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, Julian$$uUniversidad de Zaragoza
000144802 700__ $$aSwamy, Mahima
000144802 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000144802 773__ $$g(2024), [14 pp.]$$pMucosal Immunology$$tMucosal Immunology$$x1933-0219
000144802 8564_ $$s3991000$$uhttps://zaguan.unizar.es/record/144802/files/texto_completo.pdf$$yVersión publicada
000144802 8564_ $$s2357740$$uhttps://zaguan.unizar.es/record/144802/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000144802 909CO $$ooai:zaguan.unizar.es:144802$$particulos$$pdriver
000144802 951__ $$a2024-09-06-10:26:20
000144802 980__ $$aARTICLE