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Live Imaging Reveals Listeria Hijacking of E-Cadherin Recycling as It Crosses the Intestinal Barrier

37 Pages Posted: 4 Aug 2020 Publication Status: Published

See all articles by Minhee Kim

Minhee Kim

Institut Pasteur - Biology of Infection Unit

Cindy Fevre

Institut Pasteur - Biology of Infection Unit

Morgane Lavina

Institut Pasteur - Biology of Infection Unit

Olivier Disson

Institut Pasteur - Biology of Infection Unit

Marc Lecuit

Institut Pasteur - Biology of Infection Unit

More...

Abstract

Listeria monocytogenes is a foodborne bacterial pathogen that causes listeriosis, a severe systemic infection. Its translocation across the intestinal epithelium is mediated by the interaction of internalin (InlA), a Listeria surface protein, with its host species-specific receptor E-cadherin (Ecad). It occurs through goblet cells, on which Ecad is luminally accessible, via an unknown mechanism. In the absence of cell lines recapitulating this phenotype in vitro, we developed an ex vivo experimental system, based on the intraluminal microinjection of Listeria in untreated, pharmacologically-treated and genetically modified intestinal organoids. Using both live light sheet microscopy and confocal imaging, we show that Listeria translocates through goblet cells within a vacuole in an InlA- and microtubule-dependent manner. As Ecad undergoes constant apical-basal recycling, we hypothesized that Lm may transit through goblet cells by hijacking Ecad recycling pathway. Indeed, Listeria is stuck at goblet cell apex when Ecad endocytosis is blocked, and remains trapped intracellularly at the basolateral pole of goblet cells when Rab11-dependent Ecad recycling is compromised. Together, these results show that Listeria, upon docking onto its luminally accessible receptor Ecad, hijacks its recycling pathway to be transferred by transcytosis across goblet cells. Live imaging of host-pathogen interactions in organoids is a promising approach to dissect their underlying cell and molecular biology.

Keywords: Listeria, epithelial translocation, organoids, intestine, goblet cell, E-cadherin recycling, live imaging, Rab11

Suggested Citation

Kim, Minhee and Fevre, Cindy and Lavina, Morgane and Disson, Olivier and Lecuit, Marc, Live Imaging Reveals Listeria Hijacking of E-Cadherin Recycling as It Crosses the Intestinal Barrier. Available at SSRN: https://ssrn.com/abstract=3646593 or http://dx.doi.org/10.2139/ssrn.3646593
This version of the paper has not been formally peer reviewed.

Minhee Kim

Institut Pasteur - Biology of Infection Unit

Cindy Fevre

Institut Pasteur - Biology of Infection Unit

Morgane Lavina

Institut Pasteur - Biology of Infection Unit

Olivier Disson

Institut Pasteur - Biology of Infection Unit

France

Marc Lecuit (Contact Author)

Institut Pasteur - Biology of Infection Unit ( email )

France

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