Shigella flexneri Targets Human Colonic Goblet Cells by O Antigen Binding to Sialyl-Tn and Tn Antigens via Glycan-Glycan Interactions.
Elizabeth Ngoc Hoa TranChristopher J DayErin McCartneyJessica PooleEdmund TseMichael P JenningsRenato MoronaPublished in: ACS infectious diseases (2020)
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.
Keyphrases
- induced apoptosis
- endothelial cells
- cell cycle arrest
- induced pluripotent stem cells
- endoplasmic reticulum stress
- signaling pathway
- cell surface
- type diabetes
- cell death
- poor prognosis
- metabolic syndrome
- single cell
- bone marrow
- long non coding rna
- lps induced
- pi k akt
- single molecule
- glycemic control
- binding protein
- molecular dynamics simulations
- data analysis