Editors' ChoiceHost-Pathogen Interactions

Intestinal cells purge to eliminate pathogens

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Science Signaling  20 Dec 2016:
Vol. 9, Issue 459, pp. ec298
DOI: 10.1126/scisignal.aam6089

Intestinal stem cells (ISCs) proliferate to replace intestinal epithelial cells damaged by pathogens. Lee et al. found that ingestion of the insect pathogen Serratia marcescens Db11 (SmDb11) induced robust ISC proliferation in Drosophila melanogaster a day after ingestion but did not induce ISC proliferation in the first few hours immediately following ingestion. Instead, ingestion of SmDb11 caused the gut epithelium to thin within a few hours of feeding, but the epithelium regained its normal thickness within 24 hours. Epithelium thinning was characterized by the presence of large vacuoles, the accumulation of lipid droplets, and the enlargement of mitochondria in the epithelial cells, followed by the extrusion of the cytoplasm into the gut lumen. Extrusion did not induce cell death or compromise the barrier function of the gut. Infection with a strain of S. marcescens lacking the pore-forming toxin hemoylsin (Sm21C4) did not trigger epithelial thinning. Furthermore, Sm21C4-infected flies exhibited decreased survival and greater ISC proliferation at later stages of infection compared with flies infected with SmDb11, implying that cytoplasmic purging reduces pathogen-induced epithelial damage. Pseudomonas entomophila also required its pore-forming toxin, monalysin, to cause epithelial thinning. When flies lacking the conserved cyclin CycJ were fed SmDb11, the intestinal epithelium thinned but did not recover its original thickness, and CycJ mutants exhibited reduced survival following infection. Feeding SmDb11, but not Sm21C4, induced the transcription of several uncharacterized genes predicted to encode short, secreted proteins in wild-type flies but not in CycJ mutants. Expressing either of two of these genes improved the recovery from intestinal thinning in CycJ mutants. Infection with bacteria that produce pore-forming toxins also caused gut epithelial thinning in honeybees, mice, and cultured human intestinal epithelial cells. Cytoplasmic extrusion was detected in the infected human cells. These results identify a conserved mechanism by which intestinal epithelial cells respond to pore-forming toxins by purging the cells of bacteria, bacterial toxins, and damaged cellular components, all of which contribute to tissue damage (see also Bonfini and Buchon).

K.-Z. Lee, M. Lestradet, C. Socha, S. Schirmeier, A. Schmitz, C. Spenlé, O. Lefebvre, C. Keime, W. M. Yamba, R. Bou Aoun, S. Liegeois, Y. Schwab, P. Simon-Assmann, F. Dalle, D. Ferrandon, Enterocyte purge and rapid recovery is a resilience reaction of the gut epithelium to pore-forming toxin attack. Cell Host Microbe 20, 716–730 (2016). [PubMed]

A. Bonfini, N. Buchon, Pore-forming toxins trigger the purge. Cell Host Microbe 20, 693–694 (2016). [PubMed]

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