Editors' ChoiceHost-Pathogen Interactions

Gaining Entry

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Science Signaling  23 Feb 2010:
Vol. 3, Issue 110, pp. ec58
DOI: 10.1126/scisignal.3110ec58

The epithelia of the intestine serve as a barrier to pathogen entry, and this function is disrupted by inflammation. Inflammation of the mucosa is frequently associated with inflammatory hypoxia. Keely et al. found that the translocation of specific Gram-positive bacteria, such as Enterococcus faecalis, across the colon epithelial cell line CaCo-2 was increased when the cells were exposed to hypoxic conditions, despite no change in paracellular permeability (transepithelial resistance). The hypoxia-induced increase in E. faecalis translocation was specifically inhibited by an antagonist to the platelet-activating factor receptor (PTAFR, also known as PAFr). Hypoxia increased PTAFR mRNA and protein abundance in Caco-2 cells, and Ptafr transcript abundance was also increased in colon epithelial cells from a mouse model of inflammatory colitis. Knockdown of hypoxia-inducible factor 1α (HIF-1α) prevented the hypoxia-induced increase in PTAFR abundance, and knockdown of either HIF-1α or PTAFR prevented the hypoxia-mediated increase in bacterial translocation. Whether this increase in the translocation of the bacteria is pathological or a host mechanism for clearing the bacteria remains to be determined.

S. Keely, L. E. Glover, T. Weissmueller, C. F. MacManus, S. Fillon, B. Fennimore, S. P. Colgan, Hypoxia-inducible factor-dependent regulation of platelet-activating factor receptor as a route for Gram-positive bacterial translocation across epithelia. Mol. Biol. Cell 21, 538–546 (2010). [Abstract] [Full Text]

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