Salmonella Typhimurium discreet-invasion of the murine gut absorptive epithelium.

Autor: Stefan A Fattinger, Desirée Böck, Maria Letizia Di Martino, Sabrina Deuring, Pilar Samperio Ventayol, Viktor Ek, Markus Furter, Saskia Kreibich, Francesco Bosia, Anna A Müller-Hauser, Bidong D Nguyen, Manfred Rohde, Martin Pilhofer, Wolf-Dietrich Hardt, Mikael E Sellin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Pathogens, Vol 16, Iss 5, p e1008503 (2020)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1008503
Popis: Salmonella enterica serovar Typhimurium (S.Tm) infections of cultured cell lines have given rise to the ruffle model for epithelial cell invasion. According to this model, the Type-Three-Secretion-System-1 (TTSS-1) effectors SopB, SopE and SopE2 drive an explosive actin nucleation cascade, resulting in large lamellipodia- and filopodia-containing ruffles and cooperative S.Tm uptake. However, cell line experiments poorly recapitulate many of the cell and tissue features encountered in the host's gut mucosa. Here, we employed bacterial genetics and multiple imaging modalities to compare S.Tm invasion of cultured epithelial cell lines and the gut absorptive epithelium in vivo in mice. In contrast to the prevailing ruffle-model, we find that absorptive epithelial cell entry in the mouse gut occurs through "discreet-invasion". This distinct entry mode requires the conserved TTSS-1 effector SipA, involves modest elongation of local microvilli in the absence of expansive ruffles, and does not favor cooperative invasion. Discreet-invasion preferentially targets apicolateral hot spots at cell-cell junctions and shows strong dependence on local cell neighborhood. This proof-of-principle evidence challenges the current model for how S.Tm can enter gut absorptive epithelial cells in their intact in vivo context.
Databáze: Directory of Open Access Journals
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