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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
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Αρβανίτης, Χρήστος-Γεώργιος Ε.
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Thesis advisor
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Χαμηλός, Γεώργιος
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Reviewer
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Μπερτσιάς, Γεώργιος
Τσατσάνης, Χρήστος
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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.
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Language |
English |
Subject |
Human macrophages |
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Intraphagosomal ROS |
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Intraphagosomal pH |
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Phagocytosis |
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Phagosome maturation |
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Ανθρώπινα μακροφάγα |
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Μεταφορείς σιδήρου |
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Φαγοκυττάρωση |
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Ωρίμανση φαγοσώματος |
Issue date |
2023-11-24 |
Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/a/f/2/metadata-dlib-1698943081-445604-22218.tkl
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Views |
1169 |
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