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Early phase of anti-Leishmania immunity in the host skin
Máčalíková, Bára ; Leštinová, Tereza (advisor) ; Kolářová, Iva (referee)
Leishmania parasites are parasitic protozoans that cause disease called leishmaniasis, which primarily affects mammals. Throughout evolution, Leishmania has adapted to the host's immune system, using it to its advantage. This bachelor's thesis describes the relationship between Leishmania and early immune components in the host's skin, as well as the parasite's ability to inhibit the microbicidal activities of cells. The infection begins with the inoculation of infectious promastigotes into the skin, and before reaching their target cells, Leishmania primarily interacts primarily with the complement system, keratinocytes, fibroblats, eosinophils, neutrophils, mast cells and dendritic cells. Understanding the mutual interaction between the host and the parasite is essential for vaccine development and the treatment of leishmaniasis. KEYWORDS: leishmania, skin, early imunity, complement system, keratinocytes, fibroblasts, eosinophils, neutrophils, mast cells, dendritic cells
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Immunomodulatory properties of helminth-produced molecules and their effect during autoimmune and chronic inflammatory diseases
Moravcová, Johana ; Šmídová, Barbora (advisor) ; Kolářová, Iva (referee)
Parasitic helminths produce excretion/secretion products (ESP) that affect the host's immune system to prevent damage or exclusion of the parasite. In recent decades, individual ESP molecules have been the focus of research for the treatment of autoimmune and chronic inflammatory diseases due to their immunomodulatory potential. Diseases that have been investigated in this context include ulcerative colitis, multiple sclerosis, type 1 diabetes, rheumatoid arthritis and allergic asthma. Among the pleiad of helminths and their immunomodulatory molecules, it is worth mentioning Acanthocheilonema viteae (Av17), Ancylostoma caninum (NIF), Ascaris lumbricoides (Al-CPI), Brugia malayi (BMCys), Clonorchis sinensis (CsStefin-1), Fasciola hepatica (FhHDM-1), Heligmosomoides polygyrus (HpTGM), Schistosoma japonicum (SjCystatin) and Schistosoma mansoni (Omega-1). The main effects of these molecules on the host immune system include affecting the function of dendritic cells and macrophages, influencing cytokine production and reducing the Th1 immune response, which usually leads to alleviation of disease symptoms. Based on the current state of knowledge, it is not yet certain how the molecules will work in treating patients and whether they will have the same effect when administered in the long term. Despite...
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Factors affecting the protective effect provided by sand fly saliva immunization on the outcome of Leishmania infection
Jelínková, Kristýna ; Kolářová, Iva (advisor) ; Lipoldová, Marie (referee)
ENGLISH VERSION Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, transmitted by its vector - female sand flies during the process of blood feeding. Preexposure to sand fly saliva prior to Leishmania infection affects the host immune system, leading to possible establishment of protective effect on the disease outcome. This effect is based on the delayed type hypersensitivity reaction to sand fly saliva which has been shown to peak about 48 hours after antigen encounter, leading to the more effective host immune response towards the Leishmania parasites. In this project, we found this protective effect as species-specific, additionally dependent also on the timing of the infection post last immunization. Results of presented experiments showed that infection of BALB/c mice with Leishmania major performed after 48 hours post last Phlebotomus duboscqi sand fly saliva immunization, did not confer protection in comparison to infection performed at one-week after the last exposure. Moreover, the effect of the sand fly saliva pre-exposure was at this shorter timing of infection rather diminished, supported by insignificant differences in the measured parameters compared to the unpre-exposed infected control group. Additionally, immunization with sand fly Sergentomyia...
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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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Macrophages and nitric oxide in leishmania - sandfly - host interactions
Kratochvílová, Tereza ; Kolářová, Iva (advisor) ; Fialová, Anna (referee)
Leishmania reside fagolysosome of macrophages immediately after their entry to host where they multiply and consequently infect other macrophages or eventually other cells. A synthesis of a reactive reactant of oxygen and nitrogen is one of the mechanisms that some mammal cells are equipped with and that also contributes to eradication of leishmania. Nitric oxide rising during a metabolic change of L-arginine under the catalysis of NO synthase is of a large importance. Beyond cytotoxic function, nitric oxide is involved in signalling pathways for a neurotransmission (nNOS) and vasorelaxation (eNOS). Not all types of macrophages have ability to produce NO (iNOS). It is a heterogeneous group differing in immunological function and also in physiology. A group of classical activated macrophages represents an effective APC capable of efficient killing of intracellular pathogens. In addition to NO, they also secrete an inflammatory cytokines, which evolve an immune reaction towards to Th1. Contrary to this, a group of alternative activated macrophages is not capable of any efficient antigen presentation and nitric oxide production but produces L-ornithine, which is a precursor of polyamines, which leishmania utilizes for its own intracellular growth. For the mouse model, status of resistance and/or...
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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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Immunity in hosts repeatedly exposed to sand fies and the effect on pathogen transmission
Pohanková, Lucia ; Kolářová, Iva (advisor) ; Fialová, Anna (referee)
6 Abstrakt During the feeding of infected sand flies are inoculate into the host also sand fly saliva, which can strongly modulate the response of the immune system. If the host is naive, the course of infection is usually worse. In cutaneous leishmaniasis, the lesions developed early, are more destructive and persist longer. The hosts living in endemic areas of leishamniasis and their vector hosts are often exposed to feeding uninfected sand flies. For host are the saliva antigenic and induces specific cellular and antibody responses. This responses induce the protection against leishmania infection and differ for different hosts, attempts were made most frequently in murine and canine models. In humans, as hosts is difficult to monitor developments leishmania infection after previous exposure, because in humans mainly monitors the levels of antibodies, by which we can determine the degree of sand fly bites and the risk of transmission of leishmaniasis. Keywords: Lutzomyia, Phlebotomus, DTH, antibody, IgG,
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Macrophages in leishmania - sand fly - host interaction
Kratochvílová, Tereza ; Kolářová, Iva (advisor) ; Fialová, Anna (referee)
Sand flies (order Diptera) are vectors of Leishmania parasites (Trypanosomatida), which are inoculated into the host skin together with the vector saliva. Sand fly saliva plays the important role in the Leishmania transmission; in naive host it supresses the host immune response assisting Leishmania to establish the infection, while in repeatedly bitten host it elicits a protective immune response. The submitted thesis focuses on the effect of sand fly saliva on macrophages, the key cells in the infection control. In the first part of the thesis we established a laboratory model L. major - P. papatasi - Balb/c to describe the protective effect of saliva immunization on Leishmania infection development. Immunized mice were protected against Leishmania infection which was reflected in the ear lesion size, parasite load in the ear dermis and draining lymph nodes but also in cytokine production. On the contrary, produced lower amount of nitric oxide, while arginase activity was comparable with nonimmunized group. The IgG antibodies against saliva served as a marker of exposure to sandflies while IgG antibodies against Leishmania antigens served as a marker of infection severity. The experiments were aimed on the possibility of cross-protectivity in Balb/c mice against L. major between closely related...
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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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