Mechanical Competition Triggered by Innate Immune Signaling Drives The Collective Extrusion of Bacterially-Infected Epithelial Cells

Cell competition: Bridging the scales through cell-based modeling

“…While relatively intuitive, the role of stiffness differences in mechanical competition is one the most unexpected prediction of the model. This nicely fits recent data showing how bacterial infection of epithelial cells can trigger mechanical-driven cell elimination through a reduction of infected cell stiffness 20 . Given the increasing complexity of cell competition and the accumulation of pathways/mechanisms involved in cell elimination, such quantitative approaches will become more and more essential to comprehend the mechanisms that govern the long-term fate of cell populations.…”

Collective effects in epithelial cell death and cell extrusion

“…In this case the collective movements are driven by the secretion of the chemoattractant FGF21 by the Scrib KD cells [35]. Interestingly, similar movements are also required to expel epithelial cells infected by L. monocytogenes and are driven by the activation of NF-κB and the relative reduction of stiffness of the infected cells [36].…”

Borrelia burgdorferi modulates the physical forces and immunity signaling in endothelial cells

“…Given the centrality of the NFkB and TNFa signaling pathways in many types of infection and their recent involvement in modulating host cell mechanics in response to infection with intracellular bacterial pathogens (Bastounis et al, 2021), we examined in more detailed which specific genes of these two pathways were differentially expressed during Bb-exposure (Figure S6). At 4 hpe, we found that genes encoding a number of cytokines were significantly upregulated in Bb-exposed ECs, namely: CXCL2 (gene encoding the chemokine CXCL2), CXCL1 (gene encoding the chemokine CXCL1), CXCL8 (gene encoding the chemokine IL-8) and CCL2 (gene encoding the chemokine MCP1).…”

“…In addition, exposure of different host cell types to Bb activates innate immune signaling pathways such as those dependent on the transcription factor NF-kB (Dev et al, 2011). Of interest, we recently showed that activation of innate immune signaling, particularly of NF-kB, by infection can lead to dramatic changes in host cell mechanics including a decrease in traction forces of infected as compared to uninfected cells (Bastounis et al, 2021). In the context of Bb infection, a weakening in intercellular force transduction could enhance paracellular permeability favoring bacterial transmigration through the endothelium.…”