Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice
During infection, antigen-presenting cells release cytokines and eicosanoids (including leukotrienes, epoxyeicosatrienoic acids, and prostanoids) to activate adaptive immunity. Leukotrienes (LTs), an eicosanoids subset, are produced from arachidonic acid via 5- lipoxygenase metabolism, resulting in...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English English |
| Published: |
Department of Pathology
2025
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613653363064832 |
|---|---|
| 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 | During infection, antigen-presenting cells release cytokines and eicosanoids (including leukotrienes, epoxyeicosatrienoic acids, and prostanoids) to activate adaptive immunity. Leukotrienes (LTs), an eicosanoids subset, are produced from arachidonic acid via 5- lipoxygenase metabolism, resulting in LTB4 and cysteinyl LTs (cysLTs; LTC4, LTD4 and LTE4). CysLTs, which are pro-inflammatory lipid mediators, play a role in asthma and interact with three G-protein-coupled receptors (CysLTR1, CysLTR2, and GPR99). While the role of CysLTR1 and its ligand has been studied in asthmatic and allergic responses, its function during bacterial infections remains unclear. Our study aims to elucidate the role of CysLTR1 in disease progression using C57BL/6 and Balb/c mice infected either with Listeria monocytogenes (Lm) or with Mycobacterium tuberculosis (Mtb). Using CysLTR1 knockout (Cysltr1-/-) mice, we conducted time course and survival studies on both C57BL/6 and Balb/C genetic backgrounds. Our findings revealed that the function of CysLTR1 in bacterial infections is influenced by the host's genetic background and gender. Interestingly, CysLTR1 deletion did not impact survival or tissue pathology in C57BL/6 mice during Lm and Mtb infections. However, in Lm infection, CysLTR1 deletion led to increased recruitment of neutrophils to the liver and spleen, while in female Cysltr1-/- mice during Mtb infection, lung neutrophil recruitment was elevated. In Balb/C mice, CysLTR1 deletion during Lm infection affected survival in a sex-dependent manner, providing protection to females by reducing neutrophil recruitment. Conversely, Balb/C male mice were more susceptible to Lm infection. Notably, during Mtb infection, CysLTR1 deletion in Balb/C mice resulted in improved disease outcomes due to reduced lung neutrophils and pathology. In summary, CysLTR1 signalling significantly influences neutrophil recruitment and activation during intracellular bacterial infections, with its impact varying based on gender and genetic background. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/41886 |
| institution | University of Cape Town (South Africa) |
| language | English eng |
| last_indexed | 2026-06-10T12:39:34.182Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Department of Pathology |
| publisherStr | Department of Pathology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/41886 The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice Poswayo, Sibongiseni Kwakho Luntukazi Parihar, Suraj Ozturk, Mumin Brombacher, Frank Tuberculosis infections During infection, antigen-presenting cells release cytokines and eicosanoids (including leukotrienes, epoxyeicosatrienoic acids, and prostanoids) to activate adaptive immunity. Leukotrienes (LTs), an eicosanoids subset, are produced from arachidonic acid via 5- lipoxygenase metabolism, resulting in LTB4 and cysteinyl LTs (cysLTs; LTC4, LTD4 and LTE4). CysLTs, which are pro-inflammatory lipid mediators, play a role in asthma and interact with three G-protein-coupled receptors (CysLTR1, CysLTR2, and GPR99). While the role of CysLTR1 and its ligand has been studied in asthmatic and allergic responses, its function during bacterial infections remains unclear. Our study aims to elucidate the role of CysLTR1 in disease progression using C57BL/6 and Balb/c mice infected either with Listeria monocytogenes (Lm) or with Mycobacterium tuberculosis (Mtb). Using CysLTR1 knockout (Cysltr1-/-) mice, we conducted time course and survival studies on both C57BL/6 and Balb/C genetic backgrounds. Our findings revealed that the function of CysLTR1 in bacterial infections is influenced by the host's genetic background and gender. Interestingly, CysLTR1 deletion did not impact survival or tissue pathology in C57BL/6 mice during Lm and Mtb infections. However, in Lm infection, CysLTR1 deletion led to increased recruitment of neutrophils to the liver and spleen, while in female Cysltr1-/- mice during Mtb infection, lung neutrophil recruitment was elevated. In Balb/C mice, CysLTR1 deletion during Lm infection affected survival in a sex-dependent manner, providing protection to females by reducing neutrophil recruitment. Conversely, Balb/C male mice were more susceptible to Lm infection. Notably, during Mtb infection, CysLTR1 deletion in Balb/C mice resulted in improved disease outcomes due to reduced lung neutrophils and pathology. In summary, CysLTR1 signalling significantly influences neutrophil recruitment and activation during intracellular bacterial infections, with its impact varying based on gender and genetic background. 2025-09-19T12:22:05Z 2025-09-19T12:22:05Z 2025 2025-09-19T11:31:00Z Thesis / Dissertation Doctoral PhD http://hdl.handle.net/11427/41886 en eng application/pdf Department of Pathology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Tuberculosis infections Poswayo, Sibongiseni Kwakho Luntukazi The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| thesis_degree_str | Doctoral |
| title | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| title_full | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| title_fullStr | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| title_full_unstemmed | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| title_short | The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| title_sort | role of cysteinyl leukotriene type 1 receptor cysltr1 during listeria monocytogenes and mycobacterium tuberculosis infections in mice |
| topic | Tuberculosis infections |
| url | http://hdl.handle.net/11427/41886 |
| work_keys_str_mv | AT poswayosibongisenikwakholuntukazi theroleofcysteinylleukotrienetype1receptorcysltr1duringlisteriamonocytogenesandmycobacteriumtuberculosisinfectionsinmice AT poswayosibongisenikwakholuntukazi roleofcysteinylleukotrienetype1receptorcysltr1duringlisteriamonocytogenesandmycobacteriumtuberculosisinfectionsinmice |