Format

Send to

Choose Destination
Cell Host Microbe. 2009 Feb 19;5(2):123-36. doi: 10.1016/j.chom.2008.12.011.

Shigella induces mitochondrial dysfunction and cell death in nonmyleoid cells.

Author information

1
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Abstract

Shigella rapidly kills myeloid cells via a caspase-1 inflammasome-dependent cell death mechanism. However, despite a critical role for nonmyeloid cells in the physiopathology of Shigella infection, the mechanism by which Shigella kills nonmyeloid cells remains uncharacterized. Here we demonstrate that, in nonmyeloid cells, Shigella infection induces loss of mitochondrial inner membrane potential, mitochondrial damage, and necrotic cell death through a pathway dependent on Bnip3 and cyclophilin D, two molecules implicated in the host oxidative stress responses. This mitochondrial cell death mechanism was potently counterbalanced by a Nod1-dependent Rip2/IKKbeta/NF-kappaB signaling pathway activated by the pathogen in the first hours of infection. Our results suggest that in nonmyeloid cells, oxidative stress pathways and signaling triggered by an intracellular bacterial pathogen are tightly linked and demonstrate the existence of specific Shigella-induced prodeath and prosurvival pathways converging at the mitochondria to control a necrotic cell death program.

PMID:
19218084
DOI:
10.1016/j.chom.2008.12.011
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center