Relapsing fever (RF) is caused by different species of Borrelia transmitted by soft ticks or by the human body louse. Illness is characterized by reappearing peaks of high concentrations of spirochetes in blood, concordant with fever peaks separated by asymptomatic periods. Neuroborreliosis is one of the most severe manifestations of RF borreliosis. To understand the immune response during early RF, we analyzed immune cells in brain and kidney of mice infected with B. crocidurae during the acute infection. Our results indicate that brain defense is comprised primarily of innate immune cells. Despite the infiltration of innate immune cells, Borrelia was not completely eradicated. A failure of the host brain to clear the bacteria may give the pathogen a niche where it can persist. Using our mouse model, we revealed that Borrelia duttonii could persist in the mouse brain for up to 270 days, without being present in the circulation. The infection was silent with no change in host gene expression, and the spirochetes could re-enter the circulation after immunosuppression. We propose that the brain is used by the pathogen to evade host immunity and serves as a possible natural reservoir for B. duttonii, a spirochete that has rarely been found in any mammalian host other than man. Borrelia-induced complications during pregnancy have been reported, and are especially common in RF. In our established mouse model of gestational RF, we could show that the fetuses suffered from severe pathology and growth retardation, probably as a consequence of placental destruction. We could also show trans-placental transmission of the bacteria leading to neonatal RF. Surprisingly, pregnant dams had a lower bacterial load and less severe disease, showing that pregnancy has a protective effect during RF. We have used the gestational RF model to investigate host factors favoring disease resolution. Because the spleen is the primary organ responsible for trapping and removing blood-borne pathogens, we have compared temporal changes in spleen immune cell populations and cytokine/chemokine induction during the infection. Spleens of pregnant mice had earlier neutrophil infiltration, as well as faster and higher production of pro-inflammatory mediators. This rapid, robust response suggests a more effective host defense. Thus, an enhanced pro-inflammatory response during pregnancy imparts a distinct advantage in controlling the severity of relapsing fever infection.

Nanodalelės jau taikomos komerciniuose produktuose ir diegiamos į naujus diagnostikos bei gydymo metodus. Nepaisant to, jų prasiskverbimas per apsauginius organizmo barjerus, lokalizacija organizme, pasišalinimo savybės ir ilgalaikio susikaupimo rizika nėra pakankamai ištirtos. Šios žinios reikalingos tiek naujų medicinos priemonių kūrimui, tiek ir toksikologiniam produktų įvertinimui. Darbe optiniais metodais buvo tiriama puslaidininkinių nanodalelių – CdSe/ZnS-mPEG kvantinių taškų (KT) – migracija eksperimentinių gyvūnų audiniuose in vivo, įvedant juos skirtingais būdais į organizmą. Disertacijoje nagrinėjamas KT judėjimas audinių tarpląstelinėje terpėje, jų kaupimasis skirtingose ląstelėse, prasiskverbimas per kraujagyslių, odos bei placentos barjerus. Rezultatai rodo, kad KT migruoja organizme kitaip nei daugelis medicinoje taikomų organinių junginių. Į kraujotaką patekę neprasiskverbia per daugumos kraujagyslių sienelę ir nesikaupia atitinkamuose audiniuose. Tai sudaro sąlygas naudoti KT kraujotakos vaizdinimui, angiogenezės bei kraujagyslių pažaidų tyrimuose. Parodyta, kad KT audiniuose sulaikomi tankių skaidulinių pluoštų, pvz., bazinės membranos, ir tai sąlygoja jų nepatekimą į plaukų folikulus, prakaito bei riebalų liaukas, periferinius nervus, raumenines skaidulas. Tikimasi, kad šie rezultatai padės aiškintis KT pernašos per biologinius barjerus mechanizmus, leis tiksliau įvertinti jų taikymo saugumą bei praplės KT panaudojimo biomedicinoje galimybes. / Nanoparticles (NP) are already in the composition of commercial products. New methods for medical diagnostics and therapy based on NP are developed. However the mechanisms of NP penetration through protective human barriers, biodistribution in the body, clearance properties and long-term accumulation risk remain undiscovered. This knowledge is needed to optimize biomedical applications of NP and to estimate nanotoxicological effects. This thesis investigates the migration of semiconductor NP – CdSe/ZnS-mPEG quantum dots (QD) in the tissues of experimental animals in vivo by the means of optical methods. The diffusion of QD in extracellular matrix, accumulation in different cell types, and penetration through the barriers of vessel walls, skin and placenta are analyzed. Main results show, that QD migration pathways in the body are distinct form the conventional organic drugs. QD are not transferred through the wall of most blood vessels and don‘t extravasate into the tissues. It can be used for imaging of blood vessels, angiogenesis and vessel damage research. It is shown, that QD diffusion in the tissues is limited by dense tissue fiber layers, e.g. basement membrane, and it retains QD from passage to epidermis, hair follicles, dermal glands, nerves and muscle cells. These results can be used to explore the mechanisms of biological barriers, contribute to the estimation of QD safety and expand the application areas of QD in biomedicine.

Nanoparticles (NP) are already in the composition of commercial products. New methods for medical diagnostics and therapy based on NP are developed. However the mechanisms of NP penetration through protective human barriers, biodistribution in the body, clearance properties and long-term accumulation risk remain undiscovered. This knowledge is needed to optimize biomedical applications of NP and to estimate nanotoxicological effects. This thesis investigates the migration of semiconductor NP – CdSe/ZnS-mPEG quantum dots (QD) in the tissues of experimental animals in vivo by the means of optical methods. The diffusion of QD in extracellular matrix, accumulation in different cell types, and penetration through the barriers of vessel walls, skin and placenta are analyzed. Main results show, that QD migration pathways in the body are distinct form the conventional organic drugs. QD are not transferred through the wall of most blood vessels and don‘t extravasate into the tissues. It can be used for imaging of blood vessels, angiogenesis and vessel damage research. It is shown, that QD diffusion in the tissues is limited by dense tissue fiber layers, e.g. basement membrane, and it retains QD from passage to epidermis, hair follicles, dermal glands, nerves and muscle cells. These results can be used to explore the mechanisms of biological barriers, contribute to the estimation of QD safety and expand the application areas of QD in biomedicine. / Nanodalelės jau taikomos komerciniuose produktuose ir diegiamos į naujus diagnostikos bei gydymo metodus. Nepaisant to, jų prasiskverbimas per apsauginius organizmo barjerus, lokalizacija organizme, pasišalinimo savybės ir ilgalaikio susikaupimo rizika nėra pakankamai ištirtos. Šios žinios reikalingos tiek naujų medicinos priemonių kūrimui, tiek ir toksikologiniam produktų įvertinimui. Darbe optiniais metodais buvo tiriama puslaidininkinių nanodalelių – CdSe/ZnS-mPEG kvantinių taškų (KT) – migracija eksperimentinių gyvūnų audiniuose in vivo, įvedant juos skirtingais būdais į organizmą. Disertacijoje nagrinėjamas KT judėjimas audinių tarpląstelinėje terpėje, jų kaupimasis skirtingose ląstelėse, prasiskverbimas per kraujagyslių, odos bei placentos barjerus. Rezultatai rodo, kad KT migruoja organizme kitaip nei daugelis medicinoje taikomų organinių junginių. Į kraujotaką patekę neprasiskverbia per daugumos kraujagyslių sienelę ir nesikaupia atitinkamuose audiniuose. Tai sudaro sąlygas naudoti KT kraujotakos vaizdinimui, angiogenezės bei kraujagyslių pažaidų tyrimuose. Parodyta, kad KT audiniuose sulaikomi tankių skaidulinių pluoštų, pvz., bazinės membranos, ir tai sąlygoja jų nepatekimą į plaukų folikulus, prakaito bei riebalų liaukas, periferinius nervus, raumenines skaidulas. Tikimasi, kad šie rezultatai padės aiškintis KT pernašos per biologinius barjerus mechanizmus, leis tiksliau įvertinti jų taikymo saugumą bei praplės KT panaudojimo biomedicinoje galimybes.