Title Stanice NK u patogenezi kongenitalne infekcije citomegalovirusom Title (english) NK cells in pathogenesis of congenital cytomegalovirus infection Author Carmen Rožmanić Mentor Berislav Lisnić (mentor)Mentor Ilija Brizić (komentor)Committee member Natalia Kučić (predsjednik povjerenstva)Committee member Vlatka Mejaški-Bošnjak (član povjerenstva)Committee member Đurđica Cekinović Grbeša (član povjerenstva)Granter University of Rijeka Defense date and country 2024-02-19, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 61 - Medical sciences ThesaurusMESH - Medical Subject Headings )
Cytomegalovirus Infections
congenital
Cytomegalovirus Infections
genetics
Muromegalovirus
genetics
Herpesviridae Infections
congenital
Killer Cells, Natural
immunology
Immunity, Innate
Abstract Cilj istraživanja: Prirođena infekcija citomegalovirusom (CMV) najčešća je virusna
prirođena infekcija koja može uzrokovati dugotrajne neurološke posljedice. Uloga
stanica NK u nadzoru virusa tijekom prirođene infekcije CMV-om, kao i utjecaj infekcije
na imunitet posredovan stanicama NK uglavnom su slabo istraženi. Glavni cilj ovog
istraživanja je odrediti ulogu stanica NK u nadzoru citomegalovirusa i promjene u
raznovrsnim podskupinama i funkciji stanica NK inducirane citomegalovirusnom
infekcijom u modelu prirođene infekcije.
Materijali i metode: U ovom istraživanju korišten je model prirođene infekcije, u kojem
su novookoćeni miševi inficirani MCMV-om s ciljem karakterizacije funkcionalnih,
fenotipskih i transkripcijskih promjena u stanicama NK. U istraživanju smo koristili
protočnu citometriju, transkriptomske analize te druge metode molekularne biologije.
Mehanizme odgovorne za promjene u stanicama NK nakon infekcije MCMV-om odredili
smo koristeći različite genetski modificirane miševe kojima nedostaju proupalni
medijatori ili njihovi receptori na stanicama NK. Alternativno smo inaktivaciju navedenih
tipova molekula proveli upotrebom blokirajućih protutijela.
Rezultati: Pokazali smo da infekcija novookoćenih miševa MCMV-om značajno
kompromitira fenotip, sazrijevanje i funkciju stanica NK. Upalni odgovor uzrokovao je
deregulaciju izražaja brojnih transkripcijskih faktora, što je rezultiralo dugotrajno
oslabljenom funkcijom stanica NK. Uz navedeno, utvrdili smo da perinatalna infekcija
narušava proces nastajanja stanica NK u koštanoj srži, što objašnjava navedene
dugotrajne negativne efekte infekcije na njihovu djelotvornost.
Zaključak: Ovo istraživanje pokazuje da perinatalna infekcija MCMV-om uzrokuje
dugotrajnu završnu diferencijaciju stanica NK, njihovu fenotipsku i transkripcijsku
disregulaciju, te narušava funkcionalni status stanica NK.
Abstract (english) Objectives: Congenital cytomegalovirus (CMV) infection is the most common viral
congenital infection that can cause long-term neurological sequelae. The role of NK
cells in the control of MCMV during congenital infection and the impact of infection on
NK cells in the context of immunity are not investigated. The main goal of this research
is to determine the role of NK cells in the control of MCMV during perinatal infection and
the changes in NK cell compartment and their function induced by CMV infection in the
congenital infection model.
Materials and methods: In this research, we used the congenital model of MCMV
infection, in which newborn mice are infected with MCMV, to assess the functional
phenotypic and transcriptional changes in NK cells. To address the mechanism
responsible for the changes in NK cells induced by MCMV infection, we used transgenic
mice, which lack major proinflammatory mediators or receptors on NK cells, or we used
blocking antibodies for their inactivation.
Results: We found that MCMV infection of newborns severely compromised NK cell
phenotype, maturation and functionality. Inflammatory responses to infection
dysregulated the expression of major transcription factors governing NK cell fate, such
as Eomes, resulting in impaired NK cell function. Moreover, the bone marrow's capacity
to efficiently generate new NK cells was reduced, explaining the prolonged negative
effects of perinatal infection on NK cells.
Conclusion: Results of this research show that perinatal MCMV infection induces
maturation, phenotypic change and transcriptional dysregulation of NK cells. We also
showed that perinatal MCMV infection causes functional changes in NK cells.
Keywords
citomegalovirus
prirođena infekcija
stanice NK
urođena imunost
Keywords (english)
cytomegalovirus
congenital infection
inate immunity
NK cells
Language croatian URN:NBN urn:nbn:hr:184:051400 Promotion 2024 Project Number: IP-2018-01-4435 Study programme Title: Biomedicine Postgraduate (doctoral) study programme Catalog URL https://libraries.uniri.hr/cgi-bin/lb02/unilib.cgi?form=010000000199990&id=1381816001 Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Created on 2024-04-09 08:45:06
