The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice

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dc.contributor.advisorParihar, Suraj
dc.contributor.advisorOzturk, Mumin
dc.contributor.advisorBrombacher, Frank
dc.contributor.authorPoswayo, Sibongiseni Kwakho Luntukazi
dc.date.accessioned2025-09-19T12:22:05Z
dc.date.available2025-09-19T12:22:05Z
dc.date.issued2025
dc.date.updated2025-09-19T11:31:00Z
dc.description.abstractDuring 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.
dc.identifier.apacitationPoswayo, S. K. L. (2025). <i>The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice</i>. (). University of Cape Town ,Faculty of Health Sciences ,Department of Pathology. Retrieved from http://hdl.handle.net/11427/41886en_ZA
dc.identifier.chicagocitationPoswayo, Sibongiseni Kwakho Luntukazi. <i>"The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice."</i> ., University of Cape Town ,Faculty of Health Sciences ,Department of Pathology, 2025. http://hdl.handle.net/11427/41886en_ZA
dc.identifier.citationPoswayo, S.K.L. 2025. The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice. . University of Cape Town ,Faculty of Health Sciences ,Department of Pathology. http://hdl.handle.net/11427/41886en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Poswayo, Sibongiseni Kwakho Luntukazi AB - 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. DA - 2025 DB - OpenUCT DP - University of Cape Town KW - Tuberculosis infections LK - https://open.uct.ac.za PB - University of Cape Town PY - 2025 T1 - The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice TI - The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice UR - http://hdl.handle.net/11427/41886 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/41886
dc.identifier.vancouvercitationPoswayo SKL. The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice. []. University of Cape Town ,Faculty of Health Sciences ,Department of Pathology, 2025 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/41886en_ZA
dc.language.isoen
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Pathology
dc.publisher.facultyFaculty of Health Sciences
dc.publisher.institutionUniversity of Cape Town
dc.subjectTuberculosis infections
dc.titleThe role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes and mycobacterium tuberculosis infections in mice
dc.typeThesis / Dissertation
dc.type.qualificationlevelDoctoral
dc.type.qualificationlevelPhD
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