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Identifier 000460104
Title Exploring the role of iron transporter NRAMP1 in phagocytes immunity against Aspergillus fumigatus
Alternative Title Διερεύνηση του ρόλου του μεταφορέα σιδήρου NRAMP1 στην ανοσολογική απάντηση των φαγοκυττάρων έναντι του μύκητα Aspergillus fumigatus
Author Αρβανίτης, Χρήστος-Γεώργιος Ε.
Thesis advisor Χαμηλός, Γεώργιος
Reviewer Μπερτσιάς, Γεώργιος
Τσατσάνης, Χρήστος
Abstract Host defense against fungal pathogens is primarily orchestrated through evolutionarily conserved mechanisms by the innate immune system. Phagocytosis is an elegant and complex response of professional phagocytes conceptually divided into three stages: phagosome formation, maturation, and resolution. Phagosome maturation involves a series of dynamic processes that are not well characterized at molecular level in human macrophages. Airborne filamentous fungi (molds), including Aspergillus fumigatus, are major causes of respiratory diseases in a broad spectrum of patients with immune and metabolic deficiencies. Invasive mold infections (IMI) are particularly concerning due to their high mortality rates and considerable economic burden. Understanding the pathogenesis of IMI using appropriate markers for phagosome maturation is an unmet need for predicting pathology and design of new therapeutic approaches. The primary goal of my thesis was to identify markers of phagosome maturation in M-CSF human monocyte-derived macrophages upon infection with A. fumigatus emphasizing on immunofluorescence markers associated with LAPosome formation, lysosome recruitment, as well as the development of real-time assays for assessing intraphagosomal pH and ROS production. Real- time assays and phagosome maturation markers serve as powerful tools that can be instrumental in the initial characterization of phagosomes in the context of A. fumigatus infection and high-throughput human cohort projects. Next, we build upon these established protocols to investigate the molecular role of the iron transporter NRAMP1 in human macrophages in the context of A. fumigatus infection. Preliminary work from our laboratory has revealed the critical role of Malvolio, the Drosophila counterpart, in susceptibility to aspergillosis as well as the recruitment of NRAMP1 to the phagosome of human monocytes/macrophages during phagocytosis. Therefore, our research focused on exploring the functionality of NRAMP1, employing siRNA-mediated gene silencing of this transporter in human M-CSF monocyte-derived macrophages. The main finding of this project centered on the importance of the transporter on macrophage-killing activity and pave the way for potential interesting antifungal pathways which are downstream of NADPH oxidase complex as well as the role of the transporter in proton intraphagosomal balance.
Language English
Subject Human macrophages
Intraphagosomal ROS
Intraphagosomal pH
Phagocytosis
Phagosome maturation
Ανθρώπινα μακροφάγα
Μεταφορείς σιδήρου
Φαγοκυττάρωση
Ωρίμανση φαγοσώματος
Issue date 2023-11-24
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/a/f/2/metadata-dlib-1698943081-445604-22218.tkl Bookmark and Share
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