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Intracellular Release of Granzyme B Drives a Rapid Listeriolysin O‐induced T Cell Apoptosis
Author(s) -
Carrero Javier A,
Vivanco Hector,
Unanue Emil R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.860.7
Subject(s) - listeriolysin o , granzyme b , granzyme , apoptosis , microbiology and biotechnology , granzyme a , cytolysin , programmed cell death , cytosol , intracellular , biology , listeria monocytogenes , chemistry , perforin , cytotoxic t cell , biochemistry , listeria , in vitro , virulence , genetics , bacteria , gene , enzyme
The Listeria monocytogenes protein listeriolysin‐O (LLO) is a pore‐forming protein essential for bacterial virulence. LLO's major role is to allow L. monocytogenes entry into the cytosol. Recent work has shown that it also induces apoptosis of activated lymphocytes. We studied the mechanism of induction of apoptosis by LLO at the cellular level. CD4+ T cells were generated from either normal mice or mice granzyme deficient mice and treated with LLO. LLO induced apoptosis was dependent on the expression of granzyme B. In the absence of granzyme apoptosis was dramatically reduced in magnitude. Neutralization of intracellular acidification using chloroquine inhibited the rapid apoptotic death. Mice deficient in granzyme were more resistant to infection and displayed reduced apoptosis in the splenic white pulp. Thus, LLO's pore‐forming activity in acidic organelles releases proteins, such as granzymes, into the cytosol, to initiate an apoptogenic cascade that causes death from within and this process modulates the in vivo infection.