Defining the role of the pore-forming apolipoprotein L APOL7C in a Leishmania infection
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2024-09-24
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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 .
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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.