Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis
Tuberculosis has been associated with increased risk of atherosclerotic cardiovascular disease. To examine whether mycobacterial infection exacerbates atherosclerosis development in experimental conditions, we infected low-density lipoprotein receptor knockout (Ldlr-/-) mice with Mycobacterium bovis...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.607957/full |
| _version_ | 1829135830660153344 |
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| author | Moises A. Huaman Joseph E. Qualls Shinsmon Jose Stephanie M. Schmidt Anissa Moussa David G. Kuhel Eddy Konaniah Ravi K. Komaravolu Carl J. Fichtenbaum George S. Deepe David Y. Hui |
| author_facet | Moises A. Huaman Joseph E. Qualls Shinsmon Jose Stephanie M. Schmidt Anissa Moussa David G. Kuhel Eddy Konaniah Ravi K. Komaravolu Carl J. Fichtenbaum George S. Deepe David Y. Hui |
| author_sort | Moises A. Huaman |
| collection | DOAJ |
| description | Tuberculosis has been associated with increased risk of atherosclerotic cardiovascular disease. To examine whether mycobacterial infection exacerbates atherosclerosis development in experimental conditions, we infected low-density lipoprotein receptor knockout (Ldlr-/-) mice with Mycobacterium bovis Bacille-Calmette-Guérin (BCG), an attenuated strain of the Mycobacterium tuberculosis complex. Twelve-week old male Ldlr-/- mice were infected with BCG (0.3–3.0x106 colony-forming units) via the intranasal route. Mice were subsequently fed a western-type diet containing 21% fat and 0.2% cholesterol for up to 16 weeks. Age-matched uninfected Ldlr-/- mice fed with an identical diet served as controls. Atherosclerotic lesions in aorta were examined using Oil Red O staining. Changes induced by BCG infection on the immunophenotyping profile of circulating T lymphocytes and monocytes were assessed using flow cytometry. BCG infection increased atherosclerotic lesions in en face aorta after 8 weeks (plaque ratio; 0.021±0.01 vs. 0.013±0.01; p = 0.011) and 16 weeks (plaque ratio, 0.15±0.13 vs. 0.06±0.02; p = 0.003). No significant differences in plasma cholesterol or triglyceride levels were observed between infected and uninfected mice. Compared to uninfected mice, BCG infection increased systemic CD4/CD8 T cell ratio and the proportion of Ly6Clow non-classical monocytes at weeks 8 and 16. Aortic plaque ratios correlated with CD4/CD8 T cell ratios (Spearman’s rho = 0.498; p = 0.001) and the proportion of Ly6Clow non-classical monocytes (Spearman’s rho = 0.629; p < 0.001) at week 16. In conclusion, BCG infection expanded the proportion of CD4+ T cell and Ly6Clow monocytes, and aggravated atherosclerosis formation in the aortas of hyperlipidemic Ldlr-/- mice. Our results indicate that mycobacterial infection is capable of enhancing atherosclerosis development. |
| first_indexed | 2024-12-14T18:31:21Z |
| format | Article |
| id | doaj.art-bb4e7aeae6654bfcbd4ef24ab2d2321f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T18:31:21Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bb4e7aeae6654bfcbd4ef24ab2d2321f2022-12-21T22:51:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.607957607957Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates AtherosclerosisMoises A. Huaman0Joseph E. Qualls1Shinsmon Jose2Stephanie M. Schmidt3Anissa Moussa4David G. Kuhel5Eddy Konaniah6Ravi K. Komaravolu7Carl J. Fichtenbaum8George S. Deepe9David Y. Hui10Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesMetabolic Diseases Research Center, Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesMetabolic Diseases Research Center, Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesMetabolic Diseases Research Center, Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesMetabolic Diseases Research Center, Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesTuberculosis has been associated with increased risk of atherosclerotic cardiovascular disease. To examine whether mycobacterial infection exacerbates atherosclerosis development in experimental conditions, we infected low-density lipoprotein receptor knockout (Ldlr-/-) mice with Mycobacterium bovis Bacille-Calmette-Guérin (BCG), an attenuated strain of the Mycobacterium tuberculosis complex. Twelve-week old male Ldlr-/- mice were infected with BCG (0.3–3.0x106 colony-forming units) via the intranasal route. Mice were subsequently fed a western-type diet containing 21% fat and 0.2% cholesterol for up to 16 weeks. Age-matched uninfected Ldlr-/- mice fed with an identical diet served as controls. Atherosclerotic lesions in aorta were examined using Oil Red O staining. Changes induced by BCG infection on the immunophenotyping profile of circulating T lymphocytes and monocytes were assessed using flow cytometry. BCG infection increased atherosclerotic lesions in en face aorta after 8 weeks (plaque ratio; 0.021±0.01 vs. 0.013±0.01; p = 0.011) and 16 weeks (plaque ratio, 0.15±0.13 vs. 0.06±0.02; p = 0.003). No significant differences in plasma cholesterol or triglyceride levels were observed between infected and uninfected mice. Compared to uninfected mice, BCG infection increased systemic CD4/CD8 T cell ratio and the proportion of Ly6Clow non-classical monocytes at weeks 8 and 16. Aortic plaque ratios correlated with CD4/CD8 T cell ratios (Spearman’s rho = 0.498; p = 0.001) and the proportion of Ly6Clow non-classical monocytes (Spearman’s rho = 0.629; p < 0.001) at week 16. In conclusion, BCG infection expanded the proportion of CD4+ T cell and Ly6Clow monocytes, and aggravated atherosclerosis formation in the aortas of hyperlipidemic Ldlr-/- mice. Our results indicate that mycobacterial infection is capable of enhancing atherosclerosis development.https://www.frontiersin.org/articles/10.3389/fimmu.2020.607957/fullmycobacteriumBacille-Calmette-GuérintuberculosisatherosclerosisinflammationT cells |
| spellingShingle | Moises A. Huaman Joseph E. Qualls Shinsmon Jose Stephanie M. Schmidt Anissa Moussa David G. Kuhel Eddy Konaniah Ravi K. Komaravolu Carl J. Fichtenbaum George S. Deepe David Y. Hui Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis Frontiers in Immunology mycobacterium Bacille-Calmette-Guérin tuberculosis atherosclerosis inflammation T cells |
| title | Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis |
| title_full | Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis |
| title_fullStr | Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis |
| title_full_unstemmed | Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis |
| title_short | Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis |
| title_sort | mycobacterium bovis bacille calmette guerin infection aggravates atherosclerosis |
| topic | mycobacterium Bacille-Calmette-Guérin tuberculosis atherosclerosis inflammation T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.607957/full |
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