48609 20190318100446.0 doi 10.1016/j.celrep.2014.06.012 sideral 85743 ART-2014-85743 eng (orcid)0000-0002-9730-2210 Arias, MA Universidad de Zaragoza Elucidating sources and roles of Granzymes A and B during bacterial infection and sepsis 2014 Access copy available to the general public Unrestricted During bacterial sepsis, proinflammatory cytokines contribute to multiorgan failure and death in a pro- cess regulated in part by cytolytic cell granzymes. When challenged with a sublethal dose of the identi- fied mouse pathogen Brucella microti, wild-type (WT) and granzyme A (gzmA)/ mice eliminate the organism from liver and spleen in 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. In comparison, after a fatal challenge, only gzmA/ mice exhibit increased survival, which correlated with reduced proinflammatory cytokines. Depletion of natural killer (NK) cells protects WT mice from sepsis without influencing bacterial clearance and the transfer of WT, but not gzmA/ NK, cells into gzmA/ recipients restores the susceptibility to sepsis. Therefore, infection-related pathology, but not bacterial clearance, appears to require gzmA, suggesting the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen. info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2011-25390 info:eu-repo/grantAgreement/ES/INIA/RTA2010-0099 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 8.358 2014 CELL BIOLOGY 27 / 184 = 0.147 2014 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0002-5490-5177 Jiménez de Bagües, MP (orcid)0000-0001-7897-9173 Aguilo, N Universidad de Zaragoza (orcid)0000-0002-1817-4549 Menao, S Universidad de Zaragoza Hervás-Stubbs, S de Martino, A Alcaraz, A Simon, MM Froelich, CJ (orcid)0000-0003-0154-0730 Pardo, J Universidad de Zaragoza 1008 630 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Microbiología 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1000 807 Universidad de Zaragoza Dpto. Anat.Pat.Med.Leg.For.To. Area Toxicología 8, 2 (2014), 420-429 Cell Reports Cell Reports 2211-1247 1497787 http://zaguan.unizar.es/record/48609/files/texto_completo.pdf Versión publicada 123233 http://zaguan.unizar.es/record/48609/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:48609 articulos driver 2019-03-18-10:03:01 ARTICLE