The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection 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.accessioned2021-02-24T13:40:27Z
dc.date.available2021-02-24T13:40:27Z
dc.date.issued2020
dc.date.updated2021-02-24T11:29:33Z
dc.description.abstractSouth 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.
dc.identifier.apacitationPoswayo, S. K. L. (2020). <i>The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/32970en_ZA
dc.identifier.chicagocitationPoswayo, Sibongiseni Kwakho Luntukazi. <i>"The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2020. http://hdl.handle.net/11427/32970en_ZA
dc.identifier.citationPoswayo, S.K.L. 2020. The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice. . ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. http://hdl.handle.net/11427/32970en_ZA
dc.identifier.ris TY - Master Thesis AU - Poswayo, Sibongiseni Kwakho Luntukazi AB - 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. DA - 2020_ DB - OpenUCT DP - University of Cape Town KW - Clinical Science and Immunology LK - https://open.uct.ac.za PY - 2020 T1 - The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice TI - The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice UR - http://hdl.handle.net/11427/32970 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/32970
dc.identifier.vancouvercitationPoswayo SKL. The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2020 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/32970en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Clinical Laboratory Sciences
dc.publisher.facultyFaculty of Health Sciences
dc.subjectClinical Science and Immunology
dc.titleThe role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMSc
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