The effect of mechanical forces on the inflammatory response of Chlamydia-infected monocytes
Chlamydia pneumoniae is an obligate respiratory pathogen in eukaryotic cells that has been implicated as a possible causative agent of chronic diseases such as atherosclerosis and coronary heart disease. Human monocytes have been found to be the carriers of this intracellular pathogen from the lungs to atherosclerotic sites, and the bacteria has been found to persist in these cells for upto 10 days without cellular lysis. During transit, C. pneumoniae-infected monocytes in circulation are subjected to shear stress due to blood flow. It has been shown that these shear forces can affect cell adhesion dynamics and other cellular responses. The effect of mechanical stimuli on monocytes is largely under-addressed in the context of C. pneumoniae infection and atherosclerosis. We hypothesized that fluid shear stress alters the inflammatory response of C. pneumoniae-infected monocytes and contributes to immune cell recruitment to the site of tissue damage. Using an in vitro model of blood flow, we determined that physiological levels of shear stress enhances the secretion and upregulation of IL-1β in a time-dependent manner in C. pneumoniae- infected monocytes. This in turn plays a role in exacerbating the inflammatory responses during atherosclerosis. As a functional consequence, monocytes exhibit increased adhesion to cytokine activated endothelial cells under flow. Taken together, these results suggest a synergistic interaction between chemical and mechanical factors in C. pneumoniae infection and inflammation.