Elucidating Sources and Roles of Granzymes A and B during Bacterial Infection and Sepsis
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Date
2014
Authors
Arias Cabrero, Maykel AlbertoJiménez de Bagüés Picazo, María Pilar
Aguiló, Nacho
Menao, Sebastián
Hervás Stubbs, Sandra
Martino, Alba de
Alcaraz, Ana
Simon, Markus, M.
Froelich, Christopher J.
Pardo, Julián
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Journal Contribution , articleArticle
Abstract
During bacterial sepsis, proinflammatory cytokines contribute to multiorgan failure and death in a process regulated in part by cytolytic cell granzymes. When challenged with a sublethal dose of the identified 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
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Bibliographic citation
Cell Reports, 8, p. 420-429
AGROVOC subjects
InfecciónSerina
Bacteriosis