Format

Send to

Choose Destination
Cell Host Microbe. 2012 Jul 19;12(1):60-70. doi: 10.1016/j.chom.2012.06.001.

Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut.

Author information

1
Global Health Institute, School of Life Science, Ecole Polytechnique Federale de Lausanne, Switzerland.

Abstract

Typically, immune responses control the pathogen, while repair and stress pathways limit damage caused by pathogenesis. The relative contribution of damage to the outcome of pathogenesis and the mechanistic links between the immune and repair pathways are poorly understood. Here, we analyze how the entomopathogenic bacterium Pseudomonas entomophila induces irreversible damage to the Drosophila gut. We find that P. entomophila ingestion induces a global translational blockage that impairs both immune and repair programs in the fly gut. P. entomophila-induced translational inhibition is dependent on bacterial pore forming toxins and reactive oxygen species produced by the host in response to infection. Translational arrest is mediated through activation of the GCN2 kinase and inhibition of the TOR pathway as a consequence of host damage. Together, our study draws a model of pathogenesis in which bacterial inhibition of translation by excessive activation of stress responsive pathways inhibits both immune and regenerative epithelial responses.

Comment in

PMID:
22817988
DOI:
10.1016/j.chom.2012.06.001
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center