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The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice
South Africa recently experienced a Listeriosis outbreak, which was responsible for over 180 deaths, caused by an intracellular, rod-shaped bacilli called Listeria monocytogenes (LM). LM can infect both phagocytic and non-phagocytic cell types and induces its uptake by expressing internalin A and B,...
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| Format: | Thesis |
| Language: | English |
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Department of Clinical Laboratory Sciences
2021
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| _version_ | 1867613333341863936 |
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| access_status_str | Open Access |
| author | Poswayo, Sibongiseni Kwakho Luntukazi |
| author2 | Parihar, Suraj |
| author_browse | Parihar, Suraj Poswayo, Sibongiseni Kwakho Luntukazi |
| author_facet | Parihar, Suraj Poswayo, Sibongiseni Kwakho Luntukazi |
| author_sort | Poswayo, Sibongiseni Kwakho Luntukazi |
| collection | Thesis |
| description | South Africa recently experienced a Listeriosis outbreak, which was responsible for over 180 deaths, caused by an intracellular, rod-shaped bacilli called Listeria monocytogenes (LM). LM can infect both phagocytic and non-phagocytic cell types and induces its uptake by expressing internalin A and B, then secretes listeriolysin O (LLO), a virulence factor forming pores on the phagosome membrane to escape into the cytosol. Macrophages can phagocytose invading pathogens and induce innate inflammatory responses. Production of cytokines and eicosanoids by antigen presenting cells activates the adaptive immunity. Eicosanoids (epoxyeicosatreinoic acids, prostanoids and leukotrienes) are generated from metabolites of 20-carbon chained polyunsaturated fatty acids and arachidonic acid. Leukotrienes (LTs) are generated from 5- lipoxygenase-metabolism of arachidonic acid to LTB4 and cysteinyl LTs (cysLTs). CysLTs are pro-inflammatory lipids that have pathobiological functions in asthma. CysLTs function through three G-protein coupled receptors (CysLTR1, CysLTR2 and GPR99). The CysLTR1 and its ligands function has been well elucidated in asthmatic and allergic responses however, its role in bacterial infections is unknown. The aim of our study was to elucidate the role of CysLTR1 on disease progression in mice and macrophages infected with LM. In this study, we showed that CysLTR1 mRNA expression is upregulated by LM infection in WT macrophages and mice. Mice deficient of CysLTR1 had no defects at homeostasis. During time kinetic experiments with LM, CysLTR1 knockout mice displayed increased neutrophil recruitment and decreased lymphocyte cells at 3dpi, however, bacterial burdens were comparable to wild-type mice. In addition, macrophages deficient of CysLTR1 have no effect on the intracellular growth of LM. In conclusion, CysLTR1 signalling plays a role in lymphoid cell activation and neutrophilic recruitment during early LM infection, however, further studies are required to better understand the role of CysLTR1 during inflammatory responses. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/32970 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:34:28.941Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Department of Clinical Laboratory Sciences |
| publisherStr | Department of Clinical Laboratory Sciences |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/32970 The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice Poswayo, Sibongiseni Kwakho Luntukazi Parihar, Suraj Ozturk, Mumin Brombacher, Frank Clinical Science and Immunology South Africa recently experienced a Listeriosis outbreak, which was responsible for over 180 deaths, caused by an intracellular, rod-shaped bacilli called Listeria monocytogenes (LM). LM can infect both phagocytic and non-phagocytic cell types and induces its uptake by expressing internalin A and B, then secretes listeriolysin O (LLO), a virulence factor forming pores on the phagosome membrane to escape into the cytosol. Macrophages can phagocytose invading pathogens and induce innate inflammatory responses. Production of cytokines and eicosanoids by antigen presenting cells activates the adaptive immunity. Eicosanoids (epoxyeicosatreinoic acids, prostanoids and leukotrienes) are generated from metabolites of 20-carbon chained polyunsaturated fatty acids and arachidonic acid. Leukotrienes (LTs) are generated from 5- lipoxygenase-metabolism of arachidonic acid to LTB4 and cysteinyl LTs (cysLTs). CysLTs are pro-inflammatory lipids that have pathobiological functions in asthma. CysLTs function through three G-protein coupled receptors (CysLTR1, CysLTR2 and GPR99). The CysLTR1 and its ligands function has been well elucidated in asthmatic and allergic responses however, its role in bacterial infections is unknown. The aim of our study was to elucidate the role of CysLTR1 on disease progression in mice and macrophages infected with LM. In this study, we showed that CysLTR1 mRNA expression is upregulated by LM infection in WT macrophages and mice. Mice deficient of CysLTR1 had no defects at homeostasis. During time kinetic experiments with LM, CysLTR1 knockout mice displayed increased neutrophil recruitment and decreased lymphocyte cells at 3dpi, however, bacterial burdens were comparable to wild-type mice. In addition, macrophages deficient of CysLTR1 have no effect on the intracellular growth of LM. In conclusion, CysLTR1 signalling plays a role in lymphoid cell activation and neutrophilic recruitment during early LM infection, however, further studies are required to better understand the role of CysLTR1 during inflammatory responses. 2021-02-24T13:40:27Z 2021-02-24T13:40:27Z 2020 2021-02-24T11:29:33Z Master Thesis Masters MSc http://hdl.handle.net/11427/32970 eng application/pdf Department of Clinical Laboratory Sciences Faculty of Health Sciences |
| spellingShingle | Clinical Science and Immunology Poswayo, Sibongiseni Kwakho Luntukazi The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice |
| thesis_degree_str | Master's |
| title | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice |
| title_full | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice |
| title_fullStr | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice |
| title_full_unstemmed | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice |
| title_short | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice |
| title_sort | role of cysteinyl leukotriene type 1 receptor cysltr1 during listeria monocytogenes infection in mice |
| topic | Clinical Science and Immunology |
| url | http://hdl.handle.net/11427/32970 |
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