- Publikační typ
- abstrakt z konference MeSH
Leishmania rely heavily on glycans to complete their digenetic life cycle in both mammalian and phlebotomine sand fly hosts. Leishmania promastigotes secrete a proteophosphoglycan-rich gel (Promastigote Secretory Gel, PSG) that is regurgitated during transmission and can exacerbate infection in the skin. Here we explored the role of PSG from natural Leishmania-sand fly vector combinations by obtaining PSG from Leishmania (L.) major-infected Phlebotomus (P.) papatasi and P. duboscqi and L. tropica-infected P. arabicus. We found that, in addition to the vector's saliva, the PSG from L. major and L. tropica potently exacerbated cutaneous infection in BALB/c mice, improved the probability of developing a patent cutaneous lesion, parasite growth and the evolution of the lesion. Of note, the presence of PSG in the inoculum more than halved the prepatent period of cutaneous L. tropica infection from an average of 32 weeks to 13 weeks. In addition, L. major and L. tropica PSG extracted from the permissive experimental vector, Lutzomyia (Lu.) longipalpis, also exacerbated infections in mice. These results reinforce and extend the hypothesis that PSG is an important and evolutionarily conserved component of Leishmania infection that can be used to facilitate experimental infection for drug and vaccine screening.
- MeSH
- kůže účinky léků parazitologie patologie MeSH
- Leishmania major chemie MeSH
- Leishmania tropica chemie MeSH
- leishmanióza kožní parazitologie patologie MeSH
- membránové proteiny aplikace a dávkování chemie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- parazitární zátěž MeSH
- Phlebotomus parazitologie MeSH
- proteoglykany aplikace a dávkování chemie MeSH
- protozoální proteiny aplikace a dávkování chemie MeSH
- sliny MeSH
- syndrom vzplanutí nemoci MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND/OBJECTIVE: Futile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (de novo lipogenesis (DNL)), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis. METHODS: Male obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days. In epididymal WAT (eWAT), TAG synthesis and DNL were determined using in vivo2H incorporation from2H2O into tissue TAG and nuclear magnetic resonance spectroscopy. Quantitative real-time-PCR and/or immunohistochemistry and western blotting were used to determine the expression of selected genes and proteins in WAT and liver. RESULTS: The mass of WAT depots declined during cold exposure (CE). Plasma levels of TAG and non-esterified FA were decreased by day 2 but tended to normalize by day 7 of CE. TAG synthesis (reflecting TAG/FA cycle activity) gradually increased during CE. DNL decreased by day 2 of CE but increased several fold over the control values by day 7. Expression of genes involved in lipolysis, glyceroneogenesis, FA re-esterification, FA oxidation and mitochondrial biogenesis in eWAT was induced during CE. All these changes were more pronounced in obesity-resistant A/J than in B6 mice and occurred in the absence of uncoupling protein 1 in eWAT. Expression of markers of glyceroneogenesis in eWAT correlated negatively with hepatic FA synthesis by day 7 in both strains. Leptin and fibroblast growth factor 21 plasma levels were differentially affected by CE in the two mouse strains. CONCLUSIONS: Our results indicate integrated involvement of (i) TAG/FA cycling and DNL in WAT, and (ii) hepatic very-low-density lipoprotein-TAG synthesis in the control of blood lipid levels and provision of FA fuels for thermogenesis in cold. They suggest that lipogenesis in WAT contributes to a lean phenotype.
- MeSH
- bílá tuková tkáň metabolismus MeSH
- fenotyp MeSH
- hubenost genetika metabolismus MeSH
- lipogeneze genetika fyziologie MeSH
- lipoproteiny VLDL metabolismus MeSH
- metabolismus lipidů MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nízká teplota * MeSH
- obezita genetika metabolismus MeSH
- termogeneze genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Roztroušená skleróza je závažné autoimunitní onemocnění centrální nervové soustavy. Vyskytuje se s relativně vysokou prevalencí, a to především u mladých lidí. K vývoji nových léčiv je zásadní pochopení patogeneze tohoto onemocnění. Té se účastní všechny složky imunity. Zkoumány jsou především lymfocytární populace. Dříve se za hlavní příčinu roztroušené sklerózy považovala nerovnováha mezi subtypy helperských lymfocytů Th1 a Th2. V posledních letech byl ale prokázán vliv dalších buněčných elementů, jako jsou B lymfocyty, cytotoxické T lymfocyty, a byly objeveny i nové buněčné typy, regulační T lymfocyty a helperské Th17. Tento článek má za cíl přiblížit základní role jednotlivých lymfocytárních podtypů v rozvoji roztroušené sklerózy, a to se zaměřením především na regulační T lymfocyty a pomocné Th17.
Multiple sclerosis is a serious autoimmune disease of the central nervous system. It occurs with relatively high prevalence, especially in young people. It is essential to understand the pathogenesis of this disease in order to develop new treatments. All components of immunity are involved in this process but current research mainly focuses on lymphocyte populations. Previously, imbalance between subtypes of helper lymphocytes Th1 and Th2 was considered as the main cause of multiple sclerosis. Recently, the influence of other cell elements, such as B lymphocytes, cytotoxic T lymphocytes, was shown. Moreover, new cell types, regulatory T lymphocytes and helper Th17 lymphocytes, have been discovered. The aim of this article is to describe the main roles of individual lymphocyte subtypes in multiple sclerosis pathogenesis, focusing first on regulatory T lymphocytes and helper Th17 lymphocytes.
- MeSH
- adaptivní imunita * fyziologie MeSH
- B-lymfocyty fyziologie MeSH
- buňky Th17 fyziologie patologie MeSH
- lidé MeSH
- regulační T-lymfocyty fyziologie patologie MeSH
- roztroušená skleróza * etiologie MeSH
- T-lymfocyty fyziologie klasifikace patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
