Hydrodynamic regulation of monocyte inflammatory response to chlamydial infection

Date
2010
Authors
Evani, Shankar Jaikishan
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Abstract

Systemic bacterial infections elicit inflammatory response that may result in acute or chronic complications. Of interest, cells in circulation experience hydrodynamic forces that influence their function. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory cell response to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with Chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that Chlamydia-infected monocytes trigger shear-induced activation and aggregation of platelets, and also adhere to activated endothelium under flow conditions. We also found that the exposure of Chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines IL-8, IL-1 and IL-6 in a time-dependent manner, and also the expression of surface adhesion molecules such as ICAM-1. As a functional consequence, infected and sheared monocytes show increased adhesion to endothelial cells under flow. Overall, our results suggest that shear stress modulate the response due to infection, which can have important implications in the pathophysiology of systemic diseases such as septic shock or atherosclerosis.

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Integrative Biology