Biološka i molekularna karakterizacija sojeva loze III Toxoplasma gondii izolovanih u Srbiji
Biological and molecular characterization of lineage III strains Toxoplasma gondii isolated in Serbia
Author
Uzelac, Aleksandra
Mentor
Đurković-Đaković, Olgica
Committee members
Savić-Pavićević, Dušanka
Miljković, Đorđe

Nikolić, Vera

Klun, Ivana

Metadata
Show full item recordAbstract
Toxoplasma gondii, protozoa iz filuma Apikompleksa, patogeni je endoparazit svih
homeotermnih vrsta koji se prenosi ingestijom kontaminirane hrane i vode i uzročnik je
toksoplazmoze. Na osnovu podataka o visokoj globalnoj prevalenciji i saznanju da patologija
koju prouzrokuje infekcija može biti ozbiljna i kod imunokompetentne populacije, T. gondii je
po značaju za javno zdravlje rangirana kao globalnom nivou na 4., a u Evropi na 2. mesto.
Intenzitet patologije uslovljene specifičnim interakcijama sa imunskim ćelijama domaćina,
velikim se delom zasniva na genotipu parazita, kojih ima preko 300 u globalnoj cirkulaciji. Iako
su mnogi geni markeri virulencije identifikovani, fenotip virulenije je teško utvrditi isključivo
genetikom, te se istraživanja fokusiraju na mehanizame virulencije. U ovom radu je ispitana
virulencija četiri različita varijantna genotipa T. gondii loze III koja čini 25,3% populacione
strukture T. gondii u Srbiji, na in vivo modelu Swiss Webster miševa, dok su mehani...zmi ispitani
in vitro u VERO ćelijama i kroz ekspresiju gena u mozgu i slezini u ranoj i kasnoj infekciji.
Utvrđeno je da su genotipovi EQ40 I K1 intermedijarno virulentni dok su EQ39 (ToxoDB#54) i
G13 nisko virulentni. Pokazano je da su mehanizmi virulencije stopa proliferacije i litički
kapacitet, koji su posledica više metaboličke aktivnosti, pokazane kroz povišenu ekspresiju
ENO2. Ovi mehanizmi uslovljavaju intenzivan proinflamatorni odgovor koji je u ranoj infekciji
evidentan kroz povišen nivo IL-12p40 i IFN-γ mRNK u mozgu i slezini. Uprkos različitim
karakteristikama imunskog odgovora na genotipove intermedijarne i niske virulencije,
imunizovani miševi preživljavaju re-infekciju RH (ToxoDB#10) sojem, što ukazuje na to da
kvalitet imunskog odgovora ne zavisi od virulencije genotipa.
Toxoplasma gondii, the etiological agent of toxoplasmosis, is a food and waterborne
Apicomplexan protozoan endoparasite of homeothermic species transmissible by ingestion. Due
to a high global prevalence and the fact that infection can cause serious pathology in the
immunocompetent individuals, T. gondii was ranked globally as the 4th and in Europe as the 2nd
parasite of significance to public health. The severity of the pathology, which follows from
specific interactions of the parasite with immune cells, depends on the parasite’s genotype, over
300 of which circulate globally. While many virulence conferring genes have been identified, the
virulence phenotype is difficult to predict by genetics alone, thus the focus is on discovering the
underlying mechanisms. In this study, the virulence of four distinct lineage III variant genotypes,
which constitute 25% of the population structure of T. gondii in Serbia, has been determined by
cumulative mortality of Swiss Webster mice, while mech...anisms were analyzed using VERO
cells and through gene expression in the brain and the spleen in early and late infection.
Genotypes EQ40 and K1 were found to be of intermediate, while EQ39 (ToxoDB#54) and G13
were of low virulence. Virulence mechanisms included high proliferation rate and lytic capacity,
supported by enhanced metabolic activity, evident in sustained higher ENO2 expression. This
results in an intense proinflammatory response in early infection, characterized by high levels of
expression of IL-12p40 and IFN-γ mRNA in the brain and spleen. However, despite distinct
characteristics of the immune response to genotypes of different virulence, immunized mice
survived RH (ToxoDB#10) challenge, which implies that the quality of the immune response is
independent of virulence.