Peters, NathanMelo, Léon2024-12-182024-12-182024-12-16Melo, L. (2024). The role of vector-derived microbiota and co-localization in the dissemination of vector transmitted pathogens (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://hdl.handle.net/1880/120226Visceral Leishmaniasis poses significant challenges to prophylactic vaccination and treatment strategies due to the ability of Leishmania spp. parasites to disseminate from the initial site of infection in the skin to the internal organs following transmission by the bite of an infected sand fly vector. This study investigated the role of inoculation method and the vector, sand fly gut-derived microbiota in modulating the host immune response and facilitating parasite dissemination. Utilizing a novel skin prick model that closely mimics natural sand fly transmission, we explored the influence of sand fly gut-derived (SFGD) bacteria on neutrophil recruitment, IL-1β production, and parasite dissemination in both wild-type and IL-1β-deficient mice. Our findings reveal an enhanced influx of neutrophils IL-1β+ in the early stages of infection, underscoring the importance of vector-derived microbiota in shaping the initial immune response. However, the absence of a significant impact of SFGD bacteria on dissemination or parasite burden challenges the hypothesis and previously published observations that SFGD bacteria facilitate dissemination. While we observed that IL-1β deficiency did not significantly alter parasite dissemination overall, a specific increase in liver burden was observed in IL-1β-/- mice exposed to SFGD bacteria, suggesting a potential liver-specific role of IL-1β in the control of disseminated parasite burden. This study highlights the complex interplay between host, pathogen, and vector-derived factors in Leishmania pathogenesis and opens avenues for further investigation into the molecular mechanisms driving these interactions. Future research should focus on the quantification of the inoculated bacterial load during transmission, the broader impacts of SFGD bacteria on other immune cell populations, the role of the host skin microbiota, and the potential therapeutic targeting of IL-1β to mitigate visceral leishmaniasis.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.sandfly microbiotaLeishmaniaDisseminationVisceral leishmaniasisVector microbiotaIL-1BImmunologyNeutrophilsLeishmania infantumEducation--SciencesEducation--HealthImmunologymaster thesis