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

Poswayo, Sibongiseni Kwakho Luntukazi

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

Thesis / Dissertation

2025

Publisher

University of Cape Town

Department

Department of Pathology

Faculty

Faculty of Health Sciences

Abstract

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.

Keywords

Tuberculosis infections

Reference:

Collections

PhD / Doctoral

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