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A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection
Cholesterol has been shown to play important role in the pathogenesis and persistence of intracellular pathogens. Here, we modulate host cholesterol biosynthesis pathway using pharmacological agent statins, which are reversible inhibitors of HMG†CoA reductase enzyme. The aim of the study was to in...
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| Format: | Thesis |
| Language: | English |
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Division of Immunology
2015
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| _version_ | 1867613141990375424 |
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| access_status_str | Open Access |
| author | Parihar, Suraj P |
| author2 | Brombacher, Frank |
| author_browse | Brombacher, Frank Parihar, Suraj P |
| author_facet | Brombacher, Frank Parihar, Suraj P |
| author_sort | Parihar, Suraj P |
| collection | Thesis |
| description | Cholesterol has been shown to play important role in the pathogenesis and persistence of intracellular pathogens. Here, we modulate host cholesterol biosynthesis pathway using pharmacological agent statins, which are reversible inhibitors of HMG†CoA reductase enzyme. The aim of the study was to investigate the role of statins in inducing host protective responses against intracellular pathogens. We report reduced growth of Listeria monocytogenes (LM) and Mycobacterium tuberculosis (Mtb) in murine macrophages. We show prominent immunomodulatory activity induced by statins, mainly increased phagosomal maturation and autophagy resulting in decreased bacterial growth in macrophages. Subsequently, statin†treated mice showed decrease in bacterial loads, accompanied by reduced histopathology in the acute phase of infection during listeriosis and tuberculosis. Furthermore, we found decreased growth of Mtb in peripheral blood mononuclear cells (PBMC) and monocyte†derived macrophages (MDM) isolated from patients with familial hypercholesterolemia (FH) on statin therapy when compared to healthy subjects. Together, our results show that statins induces protection against Mtb in murine macrophages, mice and human mononuclear cells and monocyte†derived macrophages. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/14393 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:31:26.417Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Division of Immunology |
| publisherStr | Division of Immunology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/14393 A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection Parihar, Suraj P Brombacher, Frank Guler, Reto Listeria monocytogenes Mycobacterium tuberculosis Cholesterol has been shown to play important role in the pathogenesis and persistence of intracellular pathogens. Here, we modulate host cholesterol biosynthesis pathway using pharmacological agent statins, which are reversible inhibitors of HMG†CoA reductase enzyme. The aim of the study was to investigate the role of statins in inducing host protective responses against intracellular pathogens. We report reduced growth of Listeria monocytogenes (LM) and Mycobacterium tuberculosis (Mtb) in murine macrophages. We show prominent immunomodulatory activity induced by statins, mainly increased phagosomal maturation and autophagy resulting in decreased bacterial growth in macrophages. Subsequently, statin†treated mice showed decrease in bacterial loads, accompanied by reduced histopathology in the acute phase of infection during listeriosis and tuberculosis. Furthermore, we found decreased growth of Mtb in peripheral blood mononuclear cells (PBMC) and monocyte†derived macrophages (MDM) isolated from patients with familial hypercholesterolemia (FH) on statin therapy when compared to healthy subjects. Together, our results show that statins induces protection against Mtb in murine macrophages, mice and human mononuclear cells and monocyte†derived macrophages. 2015-10-28T05:35:18Z 2015-10-28T05:35:18Z 2011 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/14393 eng application/pdf Division of Immunology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Listeria monocytogenes Mycobacterium tuberculosis Parihar, Suraj P A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection |
| thesis_degree_str | Doctoral |
| title | A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection |
| title_full | A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection |
| title_fullStr | A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection |
| title_full_unstemmed | A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection |
| title_short | A role of statins against listeria monocytogenes and Mycobacterium tuberculosis infection |
| title_sort | role of statins against listeria monocytogenes and mycobacterium tuberculosis infection |
| topic | Listeria monocytogenes Mycobacterium tuberculosis |
| url | http://hdl.handle.net/11427/14393 |
| work_keys_str_mv | AT pariharsurajp aroleofstatinsagainstlisteriamonocytogenesandmycobacteriumtuberculosisinfection AT pariharsurajp roleofstatinsagainstlisteriamonocytogenesandmycobacteriumtuberculosisinfection |