Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment
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 t...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01287/full |
| _version_ | 1818946395780939776 |
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| author | Shankar J. Evani Shatha F. Dallo Anand K. Ramasubramanian |
| author_facet | Shankar J. Evani Shatha F. Dallo Anand K. Ramasubramanian |
| author_sort | Shankar J. Evani |
| collection | DOAJ |
| description | 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-, IL-1, 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. |
| first_indexed | 2024-12-20T08:14:20Z |
| format | Article |
| id | doaj.art-3a7e384e76054900a20f71a928624119 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T08:14:20Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-3a7e384e76054900a20f71a9286241192022-12-21T19:47:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-08-01710.3389/fmicb.2016.01287217810Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironmentShankar J. Evani0Shatha F. Dallo1Anand K. Ramasubramanian2University of Texas at San AntonioUniversity of Texas at San AntonioUniversity of Texas at San AntonioMultiple 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-, IL-1, 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01287/fullAtherosclerosisCollagen3Dendothelial dysfunctionChlamydia pneumoniaestiffness |
| spellingShingle | Shankar J. Evani Shatha F. Dallo Anand K. Ramasubramanian Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment Frontiers in Microbiology Atherosclerosis Collagen 3D endothelial dysfunction Chlamydia pneumoniae stiffness |
| title | Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment |
| title_full | Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment |
| title_fullStr | Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment |
| title_full_unstemmed | Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment |
| title_short | Biophysical and biochemical outcomes of Chlamydia pneumoniae infection promotes pro-atherogenic matrix microenvironment |
| title_sort | biophysical and biochemical outcomes of chlamydia pneumoniae infection promotes pro atherogenic matrix microenvironment |
| topic | Atherosclerosis Collagen 3D endothelial dysfunction Chlamydia pneumoniae stiffness |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01287/full |
| work_keys_str_mv | AT shankarjevani biophysicalandbiochemicaloutcomesofchlamydiapneumoniaeinfectionpromotesproatherogenicmatrixmicroenvironment AT shathafdallo biophysicalandbiochemicaloutcomesofchlamydiapneumoniaeinfectionpromotesproatherogenicmatrixmicroenvironment AT anandkramasubramanian biophysicalandbiochemicaloutcomesofchlamydiapneumoniaeinfectionpromotesproatherogenicmatrixmicroenvironment |