Elucidating sources and roles of Granzymes A and B during bacterial infection and sepsis

Arias, MA (Universidad de Zaragoza) ; Jiménez de Bagües, MP ; Aguilo, N (Universidad de Zaragoza) ; Menao, S (Universidad de Zaragoza) ; Hervás-Stubbs, S ; de Martino, A ; Alcaraz, A ; Simon, MM ; Froelich, CJ ; Pardo, J (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.celrep.2014.06.012

Año: 2014

Publicado en: Cell Reports 8, 2 (2014), 420-429
ISSN: 2211-1247

Factor impacto JCR: 8.358 (2014)

Categ. JCR: CELL BIOLOGY rank: 27 / 184 = 0.147 (2014) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/INIA/RTA2010-0099
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2011-25390

Tipo y forma: Article (Published version)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Área Inmunología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Area Toxicología (Dpto. Anat.Pat.Med.Leg.For.To.)