Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially infected epithelial cells

A Stiff Extracellular Matrix Favors the Mechanical Cell Competition that Leads to Extrusion of Bacterially-Infected Epithelial Cells

“…The third contact concerned infected cells which present weaker cell-ECM traction adhesions and therefore, we assumed their stiffness coefficients were (0,0,0.001) kPa. This distinction between infected and uninfected traction adhesion coefficients was not considered in our previous model (Bastounis et al, 2021b).…”

“…This competition between losers and winners is essential for tissue homeostasis but it also emerges during tissue development and can play a role in various pathologies including tumor development ( Meyer et al, 2014 ; Moreno et al, 2019 ). Although the chemical signals driving the battle between two different cell populations are relatively more explored, an increasing number of studies showcases that mechanical signals such as differential sensitivity to compression during cell crowding are also crucial in driving such interactions ( Gradeci et al, 2019 ; Matamoro-Vidal and Levayer, 2019 ; Moreno et al, 2019 ; Bastounis et al, 2021b ).…”

“…We recently showed that a mechanical competition during late infection drives the collective onslaught and elimination of infected cells out of the epithelial monolayer ( Bastounis et al, 2021b ). When epithelial cells in monolayer get exposed to low dosage of Listeria monocytogenes ( L.m.…”

“…Others have focused on the dynamics of intracellular bacterial spread, with the bacteria modeled as particles within two-dimensional (2-D) rigid host cells ( Ortega et al, 2019 ). Recently, we developed a computational, three-dimensional (3-D) finite element model (FEM) to explore the physical mechanisms that drive the squeezing and extrusion of bacterially infected cells during their competition with surrounding uninfected cells ( Bastounis et al, 2021b ). This simplified model not only validated our experimental results but also predicted that cell-cell adhesions between infected cells and immediate surrounders are necessary for mound formation, a result that we then confirmed experimentally.…”

Biomechanical interactions of Schistosoma mansoni eggs with vascular endothelial cells facilitate egg extravasation

“…VEC actomyosin contractility, coupled with substrate adhesion, create tensile forces that are transmitted between neighboring cells via adherens junctions, and, together, these contribute to the generation of mechanical tension at the tissue level [ 15 ]. Tensional homeostasis within cell monolayers plays a role in a wide range of processes such as shear stress mechanosensing [ 16 ], leukocyte trafficking [ 17 ], and host-pathogen interactions [ 18 , 19 ]. However, the VEC response to schistosome egg contact, and specifically whether and how VECs remodel their actomyosin cytoskeleton and actively generate mechanical forces to drive the encapsulation of eggs, are poorly understood.…”