Role of immunotherapeutic molecules in leishmaniasis

Postgraduate Thesis uoadl:2885091 370 Read counter

Unit:
Κατεύθυνση Εφαρμογές της Βιολογίας στην Ιατρική
Library of the School of Science
Deposit date:
2019-11-08
Year:
2019
Author:
Vasilakaki Athena
Supervisors info:
Αικατερίνη Γαϊτανάκη, Καθηγήτρια, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Ευδοκία Καραγκούνη, Ερευνήτρια, Α' Ελληνικό Ινστιτούτο Παστέρ
Ιωάννα Αγγελή, Επίκουρη Καθηγήτρια, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Ρόλος ανοσοθεραπευτικών ουσιών στη λεϊσμανιαση
Languages:
Greek
Translated title:
Role of immunotherapeutic molecules in leishmaniasis
Summary:
Leishmaniasis is a very severe parasitic disease that is classified as a Neglected Tropical Disease and affects millions of people every year. Leishmaniasis occurs in three clinical forms: cutaneous, mucocutaneous and visceral leishmaniasis, which is the most severe manifestation of the disease. The causative agent of leishmaniasis is the protozoan of the genus Leishmania, an obligatory intracellular parasite. The ability of the parasite to escape the host’s immune surveillance, combined with the development of resistant strains and the dubious efficacy of hitherto therapeutic approaches, makes it imperative to find alternative forms of treatment. One of the most promising approaches is immunotherapy, in particular the targeting of a specific group of molecules called immune checkpoints. This term refers to the inhibitory receptors that are expressed in the cells of the immune system and trigger signaling pathways that lead to immunosuppression. On this basis, the purpose of this study was the evaluation of the efficacy using blocking antibodies as a means of preventing the binding of the immunoregulatory molecules CD200 and CD273 (PD-L2) to their ligands, and therefore as an immunotherapeutic method for visceral leishmaniasis. At first, it was found that infection of dendritic cells with Leishmania infantum resulted in an increase of the percentage of dendritic cells that expressed CD200 and CD273 molecules, as well as in the number of those molecules on the surface of each cell. Also, it was shown that the activation of naïve CD4+ T cells from infected dendritic cells is mediated by the signaling pathway of PD-1/PD-L2, but independent of the CD200-R/CD200 pathway. On the contrary, the activation of naïve CD8+ T cells is independent of both signaling pathways. Furthermore, it was found that the CD273 blockade on infected dendritic cells, leads to inversion of the exhausted phenotype of CD4+ T cells that come from infected BALB/c mice. According to the above, the blockade of CD273 seems to be a promising therapeutical approach against leishmaniasis.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
Leishmaniasis, immunotherapy, CD200, CD273
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
91
Number of pages:
116
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