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| Identifier |
000417144 |
| Title |
The elimination pathways of Streptococcus Group Beta (GBS) in adult and neonatal macrophages and the role of Akt1 kinase |
| Alternative Title |
Τα μονοπάτια εξάλειψης του στρεπτοκόκκου Βήτα (GBS) σε ενήλικα και νεογνικά μακροφάγα και ο ρόλος της κινάσης Akt1 |
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Author
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Κολλινιάτη, Ουρανία
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Thesis advisor
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Τσατσάνης, Χρήστος
Βεργαδή, Ελένη
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| Abstract |
Streptococcus Agalactiae, also known as Streptococcus Group Beta (GBS) is an important pathogen with a wide range of host organisms, including humans. It is considered as a serious human pathogen that creates several health complications in high-risk groups, like the immunosuppressed patients, postpartum women and infants. The severity of GBS infections is extremely increased in infants where GBS is considered as the leading cause of pneumonia, sepsis and meningitis, characterized by high morbidity and mortality rates. However, there are no available vaccines to protect from all serotypes of this pathogen and therefore research of new target molecules with protective effects against GBS infections are now a necessity.
Neonates heavily exploit the defense mechanisms of innate immune system and especially macrophage activity, since their adaptive immune system is still immature. Macrophages are professional phagocytic cells of complex origin and wide diversity. They recognize extrinsic dangers and perform phagocytosis by utilizing a variety of receptor molecules that specifically bind pathogenic patterns. Based on their activation state they are distinguished as classically M1 and alternatively M2 activated cells. M1 cells display a pro-inflammatory profile, characterized by increased production of pro-inflammatory cytokines, iNOS (inducible nitric oxide synthase) and reactive oxygen species (ROS), while M2 cells have mainly anti-inflammatory responses. Key effectors of polarization process are among others Akt kinases. It is established that Ablation of Akt1 kinase polarizes cells towards the classic activation pathway (M1), while the absence of Akt2 kinase leads to the alternative activation of macrophages (M2). However in the presence of opportunistic pathogens, macrophages acquire an M1 identity and exhibit increased bactericidal capacity that leads to the efficient elimination of pathogens.
An important pathway that contributes to pathogenic organism elimination is autophagy. This process leads to the formation of double membrane organelles named autophagosomes that sequestrate harmful cargo to the lysosomes for degradation. However, during the last decade, an alternative phagocytic pathway, LC3 Associated Phagocytosis (LAP), has arisen as an immediate mechanism against pathogen infections. Unlike canonical autophagy this pathway is more rapid, highly dependent on ROS and leads to the formation of single membrane vesicles.
Although there is extended bibliography on pathogens targeted by either canonical autophagy or LAP, there are no available data on the mechanisms utilized to fight GBS infections and their efficacy in a neonatal cell stage. In the current study we tried to shed light on the specific pathways utilized by adult macrophages in the presence and in the absence of Akt1 kinase. We also sought to address how neonatal macrophages respond to GBS infection, if they display differences compared to adult cells and whether the depletion of Akt1 kinase is beneficial in terms of eliminating GBS bacteria and preventing the severe consequences that GBS infection cause. Our data are a first indication that GBS is more efficiently eliminated by Akt1-/- macrophages, probably in a ROS dependent manner and this process is related to autophagy.
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| Language |
English |
| Subject |
Neonates |
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Νεογνά |
| Issue date |
2018-07-18 |
| Collection
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School/Department--School of Medicine--Department of Medicine--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/4/b/b/metadata-dlib-1536568294-928461-28979.tkl
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| Views |
181 |
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