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Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model
Leishmaniasis is a vector-borne neglected tropical disease caused by Leishmania parasites. Approximately one million Leishmania infections are reported annually with one billion people residing in 98 countries at risk of infection. Cutaneous leishmaniasis (CL), characterized by skin lesions caused b...
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| Format: | Thesis |
| Language: | Eng |
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Department of Molecular and Cell Biology
2024
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| _version_ | 1867613170624888832 |
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| access_status_str | Open Access |
| author | Cele, Zama |
| author2 | Hurdayal, Ramona |
| author_browse | Cele, Zama Hurdayal, Ramona |
| author_facet | Hurdayal, Ramona Cele, Zama |
| author_sort | Cele, Zama |
| collection | Thesis |
| description | Leishmaniasis is a vector-borne neglected tropical disease caused by Leishmania parasites. Approximately one million Leishmania infections are reported annually with one billion people residing in 98 countries at risk of infection. Cutaneous leishmaniasis (CL), characterized by skin lesions caused by Leishmania major and other species including Leishmania tropica and Leishmania aethiopica,is the most common form of the disease. With no effective vaccine, drug treatment is fraught with complications hence leishmaniasis is a major global public health burden. Interestingly, not all infected people develop active disease showing that an in-depth understanding of immune mechanisms could allow clear criteria for developing alternate host- derived therapies. Leukotrienes (LTs), produced by macrophages and other phagocytic cells including neutrophils, mast cells and dendritic cells during arachidonic acid metabolism, are hypothesized to induce a protective response during cutaneous leishmaniasis. However, as LTs consist of cysteinyl leukotrienes (CysLTs- LTC4, LTD4, LTE4) and LTB4, it is unclear which LT subclass is responsible for this protection. Recent studies suggested treatment of cutaneous leishmaniasis infected animals with cysteinyl leukotrienes induce host protection. To investigate this further, we targeted CysLTs via one of its receptors, cysteinyl leukotriene receptor 1 (CysLTR1), for its role in resistance or susceptibility to L. major-induced CL. In male and female BALB/c mice homozygous deficient for CysLTR1, we found that disease progression, parasite burdens, antibody and cytokine responses showed no significant alteration when compared to control animals with normal CysLTR1 expression. Importantly, expression of CysLTR2 did not appear to compensate for lack of CysLTR1 in CysLTR1-/- mice. Overall, these findings indicate that CysLTR1, as a host factor, is dispensable to the non- healing response associated with CL caused by L. major in mice. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/39308 |
| institution | University of Cape Town (South Africa) |
| language | Eng |
| last_indexed | 2026-06-10T12:31:53.390Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | Department of Molecular and Cell Biology |
| publisherStr | Department of Molecular and Cell Biology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/39308 Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model Cele, Zama Hurdayal, Ramona Molecular and Cell biology Leishmaniasis is a vector-borne neglected tropical disease caused by Leishmania parasites. Approximately one million Leishmania infections are reported annually with one billion people residing in 98 countries at risk of infection. Cutaneous leishmaniasis (CL), characterized by skin lesions caused by Leishmania major and other species including Leishmania tropica and Leishmania aethiopica,is the most common form of the disease. With no effective vaccine, drug treatment is fraught with complications hence leishmaniasis is a major global public health burden. Interestingly, not all infected people develop active disease showing that an in-depth understanding of immune mechanisms could allow clear criteria for developing alternate host- derived therapies. Leukotrienes (LTs), produced by macrophages and other phagocytic cells including neutrophils, mast cells and dendritic cells during arachidonic acid metabolism, are hypothesized to induce a protective response during cutaneous leishmaniasis. However, as LTs consist of cysteinyl leukotrienes (CysLTs- LTC4, LTD4, LTE4) and LTB4, it is unclear which LT subclass is responsible for this protection. Recent studies suggested treatment of cutaneous leishmaniasis infected animals with cysteinyl leukotrienes induce host protection. To investigate this further, we targeted CysLTs via one of its receptors, cysteinyl leukotriene receptor 1 (CysLTR1), for its role in resistance or susceptibility to L. major-induced CL. In male and female BALB/c mice homozygous deficient for CysLTR1, we found that disease progression, parasite burdens, antibody and cytokine responses showed no significant alteration when compared to control animals with normal CysLTR1 expression. Importantly, expression of CysLTR2 did not appear to compensate for lack of CysLTR1 in CysLTR1-/- mice. Overall, these findings indicate that CysLTR1, as a host factor, is dispensable to the non- healing response associated with CL caused by L. major in mice. 2024-04-04T11:03:59Z 2024-04-04T11:03:59Z 2023 2024-04-04T10:51:13Z Thesis / Dissertation Masters MSc http://hdl.handle.net/11427/39308 Eng application/pdf Department of Molecular and Cell Biology Faculty of Science |
| spellingShingle | Molecular and Cell biology Cele, Zama Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| thesis_degree_str | Master's |
| title | Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| title_full | Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| title_fullStr | Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| title_full_unstemmed | Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| title_short | Cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| title_sort | cysteinyl leukotriene receptor 1 as a host determinant for susceptibility to cutaneous leishmaniasis in a mouse model |
| topic | Molecular and Cell biology |
| url | http://hdl.handle.net/11427/39308 |
| work_keys_str_mv | AT celezama cysteinylleukotrienereceptor1asahostdeterminantforsusceptibilitytocutaneousleishmaniasisinamousemodel |