The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans

Abstract

Once bound to the epithelium, pathogenic bacteria have to cross epithelial barriers to invade their human host. In order to achieve this goal, they have to destroy the adherens junctions insured by cell adhesion molecules (CAM), such as E-cadherin (E-cad). The invasive bacteria use more or less sophisticated mechanisms aimed to deregulate CAM genes expression or to modulate the cell-surface expression of CAM proteins, which are otherwise rigorously regulated by a molecular crosstalk essential for homeostasis. Apart from the repression of CAM genes, a drastic decrease in adhesion molecules on human epithelial cells can be obtained by induction of eukaryotic endoproteases named sheddases or through synthesis of their own (prokaryotic) sheddases. Cleavage of CAM by sheddases results in the release of soluble forms of CAM. The overexpression of soluble CAM in body fluids can trigger inflammation and pro-carcinogenic programming leading to tumor induction and metastasis. In addition, the reduction of the surface expression of E-cad on epithelia could be accompanied by an alteration of the anti-bacterial and anti-tumoral immune responses. This immune response dysfunction is likely to occur through the deregulation of immune cells homing, which is controlled at the level of E-cad interaction by surface molecules αE integrin (CD103) and lectin receptor KLRG1. In this review, we highlight the central role of CAM cell-surface expression during pathogenic microbial invasion, with a particular focus on bacterial-induced cleavage of E-cad. We revisit herein the rapidly growing body of evidence indicating that high levels of soluble E-cad (sE-cad) in patients’ sera could serve as biomarker of bacterial-induced diseases.

The Butyrogenic and Lactic Bacteria of the Gut Microbiota Determine the Outcome of Allogenic Hematopoietic Cell Transplant

“…In a murine model, it was found that GVHD may be inhibited by preventing CD8 + CTL migration into the Peyer's patch either by disrupting the gene encoding the CCR5 chemokine receptor or by blocking the integrin α4β7-mucosal vascular addressin (MAdCAM-1) interaction into the gut Peyer's patches (Murai et al, 2003). Since mutants in the integrin α4β7 can also affect the integrin binding to E-cadherin (Higgins et al, 2000), it remains possible that such mutants might also affect the anti-bacterial CTL immune response through aberrant homing signals that involve E-cadherin, soluble E-cadherin, CD103, and KLRG1, as previously suggested (Devaux et al, 2019).…”

“…According to the UniProt database 1 , En. faecalis also encodes a predicted htrA protein serine protease, another candidate sheddase (Devaux et al, 2019).…”

“…Propionate is also metabolized by the liver and used by hepatocytes for glucogenesis (Cummings et al, 1987;Nicholson et al, 2012). Butyrate is used by the cells of the colon and liver and targeted to their mitochondrial compartment for energy purposes (Clausen and Mortensen, 1994;Basson et al, 2000;Della Ragione et al, 2001).…”

“…Non-muscle myosin II (NMII), notably NMIIA, a key Rho kinase target, plays a role in epithelial cell-cell adhesion by controlling the local E-cadherin accumulation at the cell-cell contact ( Priya et al, 2015 ). Moreover, E-cadherin is known for being used as target receptor for several bacteria and cleavage of E-cadherin by sheddases followed by the release of soluble E-cadherin is a mechanism frequently involved in disruption of the intestinal epithelium and invasive bacteria transmigration ( Devaux et al, 2019 ). A higher risk of blood stream infection caused either by vancomycin-resistant Enterococcus or Gram-negative bacteria (e.g., Es.…”

Placental macrophages: Origin, heterogeneity, function and role in pregnancy-associated infections

“…Several molecules produced by trophoblasts are candidate to affect differentiation of placental macrophages into MGCs. They include syncytins [ 46 , 47 ], E-cadherin and IL-4, a cytokine that mediates macrophage fusion in an E-cadherin-dependent manner [ 44 , 48 ]. The functions of placental MGCs are still obscure relying on indirect evidence.…”