144802 20260217205610.0 doi 10.1016/j.mucimm.2024.08.006 sideral 139589 ART-2024-139589 eng Chawla, Amanpreet Singh Distinct cell death pathways induced by granzymes collectively protect against intestinal Salmonella infection 2024 Access copy available to the general public Unrestricted Intestinal 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. info:eu-repo/grantAgreement/ES/AEI/PID2020-113963RB-I00 info:eu-repo/grantAgreement/ES/DGA-FEDER/B29-17R info:eu-repo/grantAgreement/ES/MICINN/SAF2017-83120-C2-1-R info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 7.6 2024 IMMUNOLOGY 20 / 183 = 0.109 2024 Q1 T1 3.148 2024 Immunology and Allergy 2024 Q1 Immunology 2024 Q1 16.5 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Vandereyken, Maud Arias, Maykel (orcid)0000-0002-9730-2210 Santiago, Llipsy (orcid)0000-0002-1861-5981 Dikovskaya, Dina Nguyen, Chi Skariah, Neema Wenner, Nicolas Golovchenko, Natasha B. Thomson, Sarah J. Ondari, Edna Garzón-Tituaña, Marcela (orcid)0000-0001-6778-0636 Anderson, Christopher J. Bergkessel, Megan C. D. Hinton, Jay Edelblum, Karen L. Pardo, Julian Universidad de Zaragoza (orcid)0000-0003-0154-0730 Swamy, Mahima 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 17, 6 (2024), 1242-1255 Mucosal Immunology Mucosal Immunology 1933-0219 3991000 http://zaguan.unizar.es/record/144802/files/texto_completo.pdf Versión publicada 2357740 http://zaguan.unizar.es/record/144802/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:144802 articulos driver 2026-02-17-20:48:34 ARTICLE