Breaking the wall: Targeting of the endothelium by pathogenic bacteria

Article (PDF Available)inNature Reviews Microbiology 8(2):93-104 · February 2010with58 Reads
DOI: 10.1038/nrmicro2269 · Source: PubMed
Abstract
The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of pathogenic bacteria. Endothelial cells are actively involved in host responses to infectious agents, producing inflammatory cytokines, controlling coagulation cascades and regulating leukocyte trafficking. In this Review, a range of bacteria and bacterial toxins are used to illustrate how pathogens establish intimate interactions with endothelial cells, triggering inflammatory responses and coagulation processes and modifying endothelial cell plasma membranes and junctions to adhere to their surfaces and then invade, cross and even disrupt the endothelial barrier.

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    • "The endothelial cell (EC) monolayer of the vascular wall is a major target for pathogenic bacteria to systemically disseminate (Lemichez et al., 2010). ECs are highly mechanosensitive and respond to varying mechanical cues, including the stiffness of their extracellular matrix (ECM), by altering both their gene expression profiles and the organization of their cytoskeletons and adhesion architecture. "
    [Show abstract] [Hide abstract] ABSTRACT: 3 A Highly Quantitative Multi-Well Format Assay for Studying the Effect of Extracellular Matrix Mechanics on the Bacterial Infection of Endothelial Cells Effie Bastounis Julie A. Theriot Abstract Bacterial pathogens can cause systemic infections by disseminating from the initial focus of infection to distant organs through the blood vasculature. To colonize tissues from the bloodstream, many bacteria need to adhere to endothelial cells (ECs) that line the vessels’ inner lumen, invade them and then spread from cell to cell. ECs are highly mechanosensitive and respond to mechanical cues, including the stiffness of the matrix on which they adhere, by dynamically re-arranging their cytoskeleton, cell-cell adhesions, and adhesions to the extracellular matrix. We hypothesize that bacterial infection of ECs might also be affected by the mechanics of the host ECs, the latter being influenced by the stiffness of the matrix on which ECs reside. To test this hypothesis, we developed a novel multi-well format assay that allows assessing in a highly quantitative manner the differential effect of matrix stiffness on EC bacterial infection. We demonstrate that, using our assay, we can quantify infection efficiency through flow cytometry and microscopy, and also measure the effects of infection on EC mechanics through traction force microscopy. Our method allows for the analysis of the effect of tissue-relevant mechanics on EC infection, which is a critical step towards understanding the biomechanical interactions between ECs, their extracellular matrix and pathogenic bacteria.
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