Defining the role of the pore-forming apolipoprotein L APOL7C in a  Leishmania infection

Cedeno, Eymi

Defining the role of the pore-forming apolipoprotein L APOL7C in a Leishmania infection

dc.contributor.advisor	Canton, Johnathan
dc.contributor.advisor	Yates, Robin
dc.contributor.author	Cedeno, Eymi
dc.contributor.committeemember	Surewaard, Bas
dc.contributor.committeemember	Ousman, Shalina
dc.contributor.committeemember	Finney, Constance
dc.contributor.committeemember	Peters, Nathan
dc.date	2024-11
dc.date.accessioned	2024-10-03T16:13:28Z
dc.date.available	2024-10-03T16:13:28Z
dc.date.issued	2024-09-24
dc.description.abstract	Leishmaniasis, is a neglected tropical disease caused by infection with the intracellular parasite Leishmania. The parasite targets phagocytic cells, including dendritic cells (DCs), where it proliferates and spreads, leading to various forms of the disease, from cutaneous lesions to visceral organ damage. Despite the clinical significance, the molecular interactions between Leishmania and DCs remain largely uncharacterized. Dendritic cells, particularly conventional dendritic cells (cDCs), are pivotal in generating cytotoxic T lymphocyte (CTL) responses crucial for controlling Leishmania infections. The cross-presentation ability of cDCs has been identified as a key process in mounting these immune responses, primarily studied in murine models. However, the molecular mechanisms underlying the cross-presentation of Leishmania antigens by cDCs are still not fully elucidated. In this study, we investigated the role of apolipoprotein 7C (APOL7C), a cDC-specific pore- forming protein, in Leishmania infection. Our results show that that APOL7C, is upregulated in response to a Leishmania infection. In addition, we find that APOL7C is recruited to the parasitophorous vacuole (PV) containing Leishmania parasites, particularly in late-stage PVs and that its recruitment creates damage in the membrane of the PV. Furthermore, our data showed that APOL7C recruitment to these compartments is dependent on the NADPH oxidase and that its insertion is voltage dependent. Interestingly, this recruitment of APOL7C appears to diminish the cross-presentation of Leishmania derived antigens of our infected cell lines in our in-vitro experiments. However, in our in vivo infection model using an Apol7c-/- mice we identified differences in the immune response in mice following inoculation of the ear. Following the course of infection the absence of Apol7c -/- mice showed a decrease in ear lesion at week 7 with higher parasite burden in the dermis. These results showed the relevance of APOL7C in a Leishmania infections new insights into the molecular mechanism underlying its role .
dc.identifier.citation	Cedeno, E. (2024). Defining the role of the pore-forming apolipoprotein L APOL7C in a Leishmania infection (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/119941
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University 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.
dc.subject.classification	Immunology
dc.title	Defining the role of the pore-forming apolipoprotein L APOL7C in a Leishmania infection
dc.type	master thesis
thesis.degree.discipline	Medicine – Immunology
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.