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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Arias MA,Jiménez de Bagües MP,Aguiló N,Menao S,Hervás-Stubbs S,de Martino A,Alcaraz A,Simon MM,Froelich CJ,Pardo Jdoi
10.1016/j.celrep.2014.06.012subject
Has Abstractpub_date
2014-07-24 00:00:00pages
420-9issue
2issn
2211-1247pii
S2211-1247(14)00480-Xjournal_volume
8pub_type
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