Elucidating sources and roles of granzymes A and B during bacterial infection and sepsis.

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 Rep

journal_title

Cell reports

authors

Arias MA,Jiménez de Bagües MP,Aguiló N,Menao S,Hervás-Stubbs S,de Martino A,Alcaraz A,Simon MM,Froelich CJ,Pardo J

doi

10.1016/j.celrep.2014.06.012

subject

Has Abstract

pub_date

2014-07-24 00:00:00

pages

420-9

issue

2

issn

2211-1247

pii

S2211-1247(14)00480-X

journal_volume

8

pub_type

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