Live Imaging Reveals Listeria Hijacking of E-Cadherin Recycling as It Crosses the Intestinal Barrier.
Curr Biol
; 31(5): 1037-1047.e4, 2021 03 08.
Article
in En
| MEDLINE
| ID: mdl-33333010
ABSTRACT
Listeria monocytogenes is a foodborne bacterial pathogen that causes human listeriosis, a severe systemic infection.1 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).2-5 It occurs through goblet cells, on which Ecad is luminally accessible,6 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 membrane vacuole in an InlA- and microtubule-dependent manner. As Ecad undergoes constant apical-basal recycling,7,8 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Listeria
/
Listeriosis
/
Listeria monocytogenes
Limits:
Humans
Language:
En
Journal:
Curr Biol
Journal subject:
BIOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
France