Shigella flexneri Targets Human Colonic Goblet Cells by O Antigen Binding to Sialyl-Tn and Tn Antigens via Glycan-Glycan Interactions
Author(s)
Tran, ENH
Day, CJ
McCartney, E
Poole, J
Tse, E
Jennings, MP
Morona, R
Year published
2020
Metadata
Show full item recordAbstract
Shigella flexneri targets colonic cells in humans to initiate invasive infection processes that lead to dysentery, and direct interactions between their lipopolysaccharide O antigens and blood group A related glycans are involved in the cell adherence interactions. Here, we show that treatment with Tn and sialyl-Tn glycans, monoclonal antibodies and lectins reactive to Tn/sialyl-Tn, and luteolin (a Tn antigen synthesis inhibitor) all significantly inhibited S. flexneri adherence and invasion of cells in vitro. Surface plasmon resonance analysis showed that lipopolysaccharide O antigen had a high affinity interaction with ...
View more >Shigella flexneri targets colonic cells in humans to initiate invasive infection processes that lead to dysentery, and direct interactions between their lipopolysaccharide O antigens and blood group A related glycans are involved in the cell adherence interactions. Here, we show that treatment with Tn and sialyl-Tn glycans, monoclonal antibodies and lectins reactive to Tn/sialyl-Tn, and luteolin (a Tn antigen synthesis inhibitor) all significantly inhibited S. flexneri adherence and invasion of cells in vitro. Surface plasmon resonance analysis showed that lipopolysaccharide O antigen had a high affinity interaction with Tn/sialyl-Tn. Immunofluorescence probing of human colon tissue with antibodies detected expression of Tn/sialyl-Tn by MUC2 producing goblet cells (GCs), and S. flexneri incubated with human colon tissue colocalized with GCs. Our findings demonstrate that S. flexneri targets GCs in the human colonic crypts via glycan–glycan interactions, establishing new insight into the infection process in humans.
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View more >Shigella flexneri targets colonic cells in humans to initiate invasive infection processes that lead to dysentery, and direct interactions between their lipopolysaccharide O antigens and blood group A related glycans are involved in the cell adherence interactions. Here, we show that treatment with Tn and sialyl-Tn glycans, monoclonal antibodies and lectins reactive to Tn/sialyl-Tn, and luteolin (a Tn antigen synthesis inhibitor) all significantly inhibited S. flexneri adherence and invasion of cells in vitro. Surface plasmon resonance analysis showed that lipopolysaccharide O antigen had a high affinity interaction with Tn/sialyl-Tn. Immunofluorescence probing of human colon tissue with antibodies detected expression of Tn/sialyl-Tn by MUC2 producing goblet cells (GCs), and S. flexneri incubated with human colon tissue colocalized with GCs. Our findings demonstrate that S. flexneri targets GCs in the human colonic crypts via glycan–glycan interactions, establishing new insight into the infection process in humans.
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Journal Title
ACS Infectious Diseases
Volume
6
Issue
10
Subject
Medical microbiology
Shigella flexneri
Tn glycan
colonic crypts
glycan−glycan
goblet cells