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Larval cestodes as model organisms used in biomedicine
Vajs, Vojtěch ; Horák, Petr (advisor) ; Kolářová, Iva (referee)
Both species of tapeworm, Taenia crassiceps and Mesocestoides corti, are used in biomedical research. Their exceptional attributes make them suitable model organisms for various forms of neurocysticercosis. Moreover, their ability to affect the metabolism and immunity of their hosts represents a potential cure for various autoimmune diseases, such as type 1 diabetes or multiple sclerosis, and various types of cancer, such as melanoma or breast cancer. The immunomodulatory capabilities of helminths and their mechanisms, which have been known for some time already, have recently commanded researchers' attention to their effect on the host organism's inflammatory reactions, including the enhancing impact of their products on the immune response. Current research is seeking to reveal the effects and underlying mechanisms of these helminth abilities and to discover further diseases, in which they could be applied. This review summarizes the reasons these cestodes are used as models, the effects of cestode infection on the host organism, and their use in neurocysticercosis study. Also, various examples where primarily T. crassiceps shows to be a potential candidate for the development of new treatments or the improvement of those already in use will be mentioned. Key words: Taenia crassiceps,...
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Genetic regulation of Leishmania infection
Sohrabi, Yahya ; Lipoldová, Marie (advisor) ; Krulová, Magdaléna (referee) ; Kolářová, Iva (referee)
6 Abstract Leishmaniasis is a neglected tropical disease, which belongs to the top health problems because it is endemic in 98 countries in Asia, Africa, the Americas and the Mediterranean region, and is gradually expanding to new areas, including Central Europe and USA. Clinical manifestations of leishmaniasis include a diverse range of forms, ranging from non-lethal cutaneous leishmaniasis to potentially lethal visceral leishmaniasis. Asymptomatic cases are known to exist in endemic areas. Different species of Leishmania induce distinct symptoms, but even the patients infected by the same species develop different symptoms and may respond differently to the treatment. Thus, one of the challenges is to explain the observed variability of leishmaniasis that cannot be attributed to the currently known factors. To find novel regulatory factors of the disease we tested molecules that were shown to play role in other infections and mapped loci controlling parasite load after L. major infection. We also determined genetic control of survival after infection with tick-borne encephalitis virus (TBEV) in order to establish whether there are common elements in response to L. major and TBEV. Interferon-induced GTPases (guanylate-binding proteins, GBPs) play an important role in inflammasome activation and mediate...
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Interactions of human immune system with saliva of bloodfeeding Nematocera
Jelínková, Kristýna ; Kolářová, Iva (advisor) ; Janda, Jozef (referee)
In humans, the bites of bloodfeeding insects from the suborder Nematocera induce an immune reaction, both humoral and cell-mediated. Some antigens presented in the saliva of some insect families - Psychodidae, Culicidae, Simuliidae and Ceratopogonidae - are studied more deeply to reveal their immunomodulatory and antigennic properties. Most studies are focused on mosquitos (Culicidae) and sand flies (Psychodidae). Mosquito saliva elicits primarily IgG and IgE antibodies. The level of antibodies in the sera of bitten individuals reflects the length and intensitity of previous exposure to insect bites. Anti-saliva IgE antibodies play an important role in response to the mosquito bites and are frequently associated with allergic reactions. On the other hand, sand fly saliva elicits primarily IgG antibodies. Cell-mediated human immune response to mosquito bites is a neglected research topic. It has been proven that the saliva of sand flies (genus Phlebotomus and Lutzomyia) stimulates proliferation of PBMC from repeatedly bitten humans. Cytokine production by human PBMC and expression of costimulatory molecules in human monocytes, macrophages, and dendritic cells are also influenced by the presence of sand fly saliva. So far as we know, there are only few studies on human immune response to black fly...
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Helminths as causative agents of vertebrate cancers
Schreiber, Manfred ; Horák, Petr (advisor) ; Kolářová, Iva (referee)
Opisthorchis viverrini, Clonorchis sinensis, and Schistosoma haematobium have been classified as the group 1 of carcinogens by the International Agency for Research on Cancer. Infections with opisthorchid flukes may lead to the development of cholangiocarcinoma of the liver, and those with schistosomes to the squamous carcinoma of the bladder. The link between helminth infections and carcinomas has been confirmed, and the exact mechanisms of carcinoma induction are at present intensively studied. There are some other representatives of helminths that are probably associated with cancers, but their direct effect on the process of carcinogenesis has not been confirmed yet. The formation of tumors can also occur via malignant transformation of totipotent parasite cells that become invasive and metastasize to different parts of the host body. However, some types of helminths may exhibit an opposite effect and show an anti-tumor activity. This review primarily focuses on the helminths associated with the development of cancer and the currently described mechanisms of carcinogenesis caused by such infections.
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Genotype influence on development of infections caused by Trypanosomatidae in mouse
Šíma, Matyáš ; Lipoldová, Marie (advisor) ; Krulová, Magdaléna (referee) ; Kolářová, Iva (referee)
Parasitic protists of genera Trypanosoma and Leishmania are members of Trypanosomatidae family. In our studies, we investigated genetic influence on infections caused by these parasites in a mouse model. These diseases are on genetic level controlled by quantitative trait loci (QTLs), when the resulting phenotype is controlled by set of genes with small individual effect. As a mouse model for mapping of QTLs controlling these infections, we used recombinant congenic strains (RCS). Each RCS carry unique set of 12.5% of the genome from donor parental strain on genetic background of other parental strain. For mapping of QTLs controlling infections caused by Trypanosoma brucei brucei (T. b. brucei) and Leishmania tropica (L. tropica) and eosinophil infiltration into inguinal lymph nodes after Leishmania major (L. major) infection, we used RCS from CcS/Dem series, where STS is donor strain and BALB/cHeA is strain of genetic background. First, it was necessary to find suitable model strains for mapping. In all three studies, we selected RCS, which exceeded range of monitored phenotype parameters in comparison with any other tested RCS or parental strains. Mice of RCS CcS-11 showed shorter survival after T. b. brucei infection and strain CcS-9 exhibited higher eosinophil infiltration after L. major infection. For...
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Surface glycoconjugates of Leishmania parasites and their interactions with immune system of vertebrate host
Pacáková, Lenka ; Leštinová, Tereza (advisor) ; Kolářová, Iva (referee)
musí po vstupu do obratlovčího hostitele čelit obranným mechanismům hostitelské imunity a proniknout do cílové buňky - pokračuje. Evoluční strategií leishmanií vyvinutou k přelstění imunitního systému Mezi nejvýznamnější povrchové glykokonjugáty patří membránově vázané proteofosfoglykany a metaloproteáz lním účinkům produktů neutrofilů a zprostředk vazbu na makrofágy. Intracelulárně pak modulují signalizační dráhy, které vedou k produkci cytokinů, směřujících polarizaci imunitní odpovědi ve prospěch Th2. Výsledkem tohoto přesměrování je vyhnutí se účinkům toxického NO, čímž je ustanovena chronicita infekce. Glykokonjugáty jsou zkoumány jako účinná složka chránících obratlovce před nákazou či bránících zpětnému přenosu čímž dalšímu šíření infekce. Klíčová slova: leishmanie, lipofosfoglykan, glykoinositolfosfolipid, proteofosfoglykan, gp63, imunitní odpověď, makrofág
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Identification, expression, and characterization of Phlebotomus orientalis salivary antigens
Šíma, Michal ; Kolářová, Iva (advisor) ; Gomes, Regis (referee) ; Chmelař, Jindřich (referee)
Sand flies (Diptera: Psychodidae) are vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae), medically and veterinary important parasites causing leishmaniasis. These protozoans are inoculated into the host during blood-feeding together with the vector saliva. Salivary components are crucial for sand fly female blood-sucking but also play a major role in the initial stage of parasite development. It was demonstrated that this rich mixture of proteins performs different functions after its injection into the host like hydrolyzing ATP and ADP, binding biogenic amines, and others which inhibits the haemostatic reaction and modulate the immune system thus enables the successful feeding. So far, cDNA salivary transcriptomes have been constructed for twelve sand fly species and we added another one - Phlebotomus orientalis, the main vector of Leishmania donovani, a causative agent of human visceral leishmaniasis in East African countries. We described members of thirteen protein families which corresponded with previously published salivary cDNA libraries of other sand fly species and showed the main salivary antigens using sera of experimentally bitten mice and naturally exposed dogs. Specific IgG antibody response is induced against sand fly salivary proteins in repeatedly bitten hosts....
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Cellular and humoral host immune response to sand fly saliva
Leštinová, Tereza ; Kolářová, Iva (advisor) ; Kopecký, Jan (referee) ; Teixeira, Clarissa Romero (referee)
Sand flies (Diptera: Phlebotominae) are bloodfeeding insects serving as vectors of Leishmania parasites (Kinetoplastida). Sand flies possess salivary glands with pharmacologically active molecules that provide them with an effective weapon against the host defence and that play an important role in Leishmania infection development. During the bloodfeeding, sand fly saliva is inoculated into the feeding site. Repeated exposures induce saliva-specific immune response, both humoral and cell-mediated. While anti-saliva antibody response correlates with the intensity of exposure and can be used as a marker of exposure, specific cellular immunity provide protection against leishmaniasis in some vector-parasite- host combinations. Sand flies differ in composition of the saliva and thus the elicited immunity is species-specific. This species-specific variability makes difficult the development of one saliva-based vaccine applicable to different Leishmania-vector combinations. However, saliva composition is more conserved among closely-related vector species, which may evoke cross-protection in bitten and subsequently infected hosts. We focused on cross-reactive properties of saliva from Phlebotomus papatasi and Phlebotomus duboscqi, the two natural vectors of Leishmania major. We demonstrated that...
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