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Toxin and xenobiotics-induced purge and subsequent recovery of enterocytes

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The intestine is a critical interface with the environment. By feeding, animals get exposed to toxins or toxicants contaminating nutrients.

We have discovered a novel stress response of Drosophila enterocytes: pore-forming toxin (S. marcescens hemolysin) or xenobiotics trigger a limited extrusion of apical cytoplasm and damaged organelles, possibly along with the toxicant, thus yielding a homogenously thin intestinal epithelium. There is no increased enterocyte cell death in the process.

The enterocytes then recover their original shape and volume in 6-9 hours by a noncell-autonomous process. This response protects enterocytes from occasional intoxications from microbial or environmental origin present in contaminated food. This protective response thus involves two distinct phases. First occurs a massive extrusion of cytoplasm that does not lyse it, the purge; next, a fast recovery phase takes place allowing the intestinal epithelium to regain its original thickness and morphology. We showed that this mechanism is conserved in Mammals. This work has been published (Cell Host Microbe, 2016). We currently try to decipher the molecular mechanisms underlying the different phases of the process.

Above, two videos of the cytoplasmic purge on the human epithelial cell line Caco-2 (the basal pole is at the top, and the apical pole is at the bottom).

 

Opposite, the video shows the cytoplasmic purge in vivo by the intestinal cells of Drosophila (the basal pole is at the bottom).

Interestingly, we have demonstrated that this process of cytoplasmic extrusion coupled with rapid recovery is also induced by hemolysin in bees, mice and human intestinal cells in culture.

These results were published in the journal Cell Host and Microbe: See following link (see also the CNRS press release).