Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes.
Cell
; 157(6): 1309-1323, 2014 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-24906149
ABSTRACT
When killer lymphocytes recognize infected cells, perforin delivers cytotoxic proteases (granzymes) into the target cell to trigger apoptosis. What happens to intracellular bacteria during this process is unclear. Human, but not rodent, cytotoxic granules also contain granulysin, an antimicrobial peptide. Here, we show that granulysin delivers granzymes into bacteria to kill diverse bacterial strains. In Escherichia coli, granzymes cleave electron transport chain complex I and oxidative stress defense proteins, generating reactive oxygen species (ROS) that rapidly kill bacteria. ROS scavengers and bacterial antioxidant protein overexpression inhibit bacterial death. Bacteria overexpressing a GzmB-uncleavable mutant of the complex I subunit nuoF or strains that lack complex I still die, but more slowly, suggesting that granzymes disrupt multiple vital bacterial pathways. Mice expressing transgenic granulysin are better able to clear Listeria monocytogenes. Thus killer cells play an unexpected role in bacterial defense.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus
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Infecções Bacterianas
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Leucócitos Mononucleares
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Antígenos de Diferenciação de Linfócitos T
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Escherichia coli
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Listeria monocytogenes
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article