Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 11, Pages 2263-2277Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110560
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Funding
- EU
- Institut Pasteur
- Institut National de la Sante et de la Recherche Medicale
- Fondation pour la Recherche Medicale
- Ville de Paris
- Fondation BNP Paribas
- European Research Council
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Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.
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