Shear stress upregulates IL‐1β secretion by <i>Chlamydia pneumoniae‐</i> infected monocytes

Cheeniyil, Aswathi; Evani, Shankar J.; Dallo, Shatha F.; Ramasubramanian, Anand K.

doi:10.1002/bit.25486

Cited by 3 publications

(3 citation statements)

References 25 publications

(33 reference statements)

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“…Monocytes infected with heat-killed chlamydial EBs show similar viability pattern to those of monocytes infected with live organisms with decrease in viability as early as 3 days ( Figure 1A ). Using confocal microscopy, we observed that at least 80% of the cells were infected and, consistent with our previous findings, the size of the inclusions ranged from very small to large inclusions (3–30 μm), and the cells contained a variable number of inclusions ( Figure 1B ) ( Cheeniyil et al, 2015 ). Interestingly, C. pneumoniae can be seen outside cells in the matrices at the end of 1 week possibly due to the release of C. pneumoniae inclusions, which correlates with the decrease in viability of infected cells in 7 days.…”

Section: Resultssupporting

confidence: 90%

Biophysical and Biochemical Outcomes of Chlamydia pneumoniae Infection Promotes Pro-atherogenic Matrix Microenvironment

2016

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Multiple studies support the hypothesis that infectious agents may be involved in the pathogenesis of atherosclerosis. Chlamydia pneumoniae is strongly implicated in atherosclerosis, but the precise role has been underestimated and poorly understood due to the complexity of the disease process. In this work, we test the hypothesis that C. pneumoniae-infected macrophages lodged in the subendothelial matrix contribute to atherogenesis through pro-inflammatory factors and by cell-matrix interactions. To test this hypothesis, we used a 3D infection model with freshly isolated PBMC infected with live C. pneumoniae and chlamydial antigens encapsulated in a collagen matrix, and analyzed the inflammatory responses over 7 days. We observed that infection significantly upregulates the secretion of cytokines TNF-α, IL-1β, IL-8, MCP-1, MMP, oxidative stress, transendothelial permeability, and LDL uptake. We also observed that infected macrophages form clusters, and substantially modify the microstructure and mechanical properties of the extracellular matrix to an atherogenic phenotype. Together, our data demonstrates that C. pneumoniae-infection drives a low-grade, sustained inflammation that may predispose in the transformation to atherosclerotic foci.

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Section: Resultssupporting

confidence: 90%

Biophysical and Biochemical Outcomes of Chlamydia pneumoniae Infection Promotes Pro-atherogenic Matrix Microenvironment

2016

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“…We observed that an MOI 1 was sufficient to see bacteria in >90% of cells, and within 8 h of infection, chlamydia was visible ( Fig. 1A ) 20 . It has previously been shown that C. pneumoniae infection increases the adhesion of monocytes to endothelium under static conditions, though it is now well established that the mechanics of adhesion under physiological flow conditions can be very different 21 .…”

Section: Resultsmentioning

confidence: 81%

“…We evaluated the effect of C. pneumoniae infection under flow on the interaction monocytes with endothelial cells and also the major endothelial adhesion receptor, E-selectin. All experiments were performed on monocytes infected for 8 h during which infection is established and a strong proinflammatory response is observed in vitro 20 . We perfused monocytes at a shear stress of 1 dyn/cm 2 for 5 min over E-selectin and TNFα-activated aortic endothelium, and assessed the number of rolling cells per unit time.…”

Section: Resultsmentioning

confidence: 99%

Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

Evani

Ramasubramanian

2016

Sci Rep

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Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

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Role for Mechanotransduction in Macrophage and Dendritic Cell Immunobiology

Mennens

Dries

Cambi

2017

Results and Problems in Cell Differentiation

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Tissue homeostasis is not only controlled by biochemical signals but also through mechanical forces that act on cells. Yet, while it has long been known that biochemical signals have profound effects on cell biology, the importance of mechanical forces has only been recognized much more recently. The types of mechanical stress that cells experience include stretch, compression, and shear stress, which are mainly induced by the extracellular matrix, cell-cell contacts, and fluid flow. Importantly, macroscale tissue deformation through stretch or compression also affects cellular function.Immune cells such as macrophages and dendritic cells are present in almost all peripheral tissues, and monocytes populate the vasculature throughout the body. These cells are unique in the sense that they are subject to a large variety of different mechanical environments, and it is therefore not surprising that key immune effector functions are altered by mechanical stimuli. In this chapter, we describe the different types of mechanical signals that cells encounter within the body and review the current knowledge on the role of mechanical signals in regulating macrophage, monocyte, and dendritic cell function.

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Shear stress upregulates IL‐1β secretion by Chlamydia pneumoniae‐ infected monocytes

Cited by 3 publications

References 25 publications

Biophysical and Biochemical Outcomes of Chlamydia pneumoniae Infection Promotes Pro-atherogenic Matrix Microenvironment

Biophysical and Biochemical Outcomes of Chlamydia pneumoniae Infection Promotes Pro-atherogenic Matrix Microenvironment

Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

Role for Mechanotransduction in Macrophage and Dendritic Cell Immunobiology

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