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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš ; Horák, Petr (advisor) ; Bilej, Martin (referee) ; Schabussova, Irma (referee)
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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Parasite-induced apoptosis in mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Parohová, Irena ; Macháček, Tomáš (advisor) ; Kopecký, Jan (referee)
Helminths are capable of induction of apoptosis in host immune cells and thus supress or dampen the host immune response. Nevertheless, apoptosis can affect also other, non-immune cells present in the infected tissues which contributes to the pathology related to the infection. Schistosomes are known to be potent immunomodulators, able to dampen the immune response of the host through induction of apoptosis, which ensures their survival. In the case of mice infected with the avian neuropathogenic T. regenti, the host immune response is responsible for parasite elimination. Therefore it seems that T. regenti can not effectively alter the immune response. On the contrary, parasite induced apoptosis in host cells present in the tissues infected with T. regenti could contribute to pathology. Thus we decided to investigate if T. regenti is capable of induction of apoptosis in infected mice. Firstly, we used TUNEL assay to detect DNA fragmentation in infected tissues. We demonstrated that DNA fragmentation is present in the infected skin 8, 24 a 48 days post infection and spinal cord 14 days post infection. Moreover, the transcriptomic analysis of the infected spinal cords revealed up-regulated expression of pro-apoptotic genes. These observations indicate possible apoptosis of host cells due to the...
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Immune response against skin-penetrating helminths with a focus on schistosomes
Revalová, Alena ; Macháček, Tomáš (advisor) ; Leštinová, Tereza (referee)
Breaching the vertebrate skin and overcoming the local immunity represents a critical step in the life cycles of many helminths. This bachelor thesis summarized the current knowledge of the skin immune response against schistosomes. Both innate and adaptive immune mechanisms are activated soon after the infection. Despite certain differences between mice and humans, complement, granulocytes and especially CD4+ T-lymphocytes are considered as key players in anti-schistosomal immunity of both species. However, several aspects of the host immune response, such as the initial source of cytokine IL-4, IL-10 or expression pattern of certain co- receptors remain unclear and warrant further research. A comprehensive understanding of the host immune response in the skin as well as the respective parasite immune evasion strategies is needed to boost vaccine development. Keywords: immune response, skin, lymph nodes, helminths, schistosomes
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The role of nitric oxide in mice infected with Trichobilharzia regenti, the neuropathogenic schistosome
Šmídová, Barbora ; Macháček, Tomáš (advisor) ; Panská, Lucie (referee)
Nitric oxide (NO) has been proved to reduce parasite burden in vertebrates infected with Schistosoma, Fasciola, Brugia or Taenia. NO negatively influences parasite growth and development, which then leads to smaller parasite-caused damage to the liver during schistosomosis and stimulates healing processes in muscles infected with Toxocara canis. Peroxynitrite, formed from NO and superoxide, significantly reduces the viability of F. hepatica adults. In case of T. regenti, the neuropathogenic schistosome, the cells capable of NO production (macrophages, neutrophils, eosinophils, microglia and astrocytes) migrate to the site of the infection suggesting that NO might affect T. regenti infection as well. Therefore, the production of NO and its effect on the course of the infection was examined in vivo and the effect of peroxynitrite on T. regenti schistosomula was examined in vitro to assess the role of reactive nitrogen species during the infection. Our results from in vivo experiments demonstrate that although the infection did not significantly elevate nitrite/nitrate results in the sera, NO is locally produced in the early stages of the infection in both the skin and the spinal cord as shown by immunohistochemical detection of inducible NO synthase. Diminishing NO production by aminoguanidine...
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Evolution of immune response driven by increasing pathogen virulence
Hančová, Klára ; Vinkler, Michal (advisor) ; Macháček, Tomáš (referee)
Coevolution is relationship between two or more species reciprocally affect each other's evolution. Coevolution is also known as host-parasite interaction where parasite becomes the driving force of host evolution. In an effort to escape the parasite, hosts create different mechanisms that protect themself from infection or minimize its impact. This text is written to acquaint the reader with the host-parasite interaction in response to improving parasite. In systems with myxoma virus and Mycoplasma gallisepticum are described changes of virulence and manipulation with host immune response. Myxomatosis should be known for its increasing virulence because of horizontal transmission. But after many years coevolution between European rabbit (Oryctolagus cuniculus) settled on low value in three different places. Second system represents young evolution between mycoplasma and house finch (Haemorhous mexicanus) which offer opportunity to watch new beggining of defense mechanism against parasite.
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Immunomodulatory properties of TES
Holečková, Markéta ; Hrdý, Jiří (advisor) ; Macháček, Tomáš (referee)
Toxocara canis and Toxocara cati are parasitic roundworms. Their definite hosts are canines or felines. Human infection is also possible and in that case these parasites cause human toxocariasis. Larvae of Toxocara spp. in the host release proteins called TES (Toxocara Excretory-Secretory antigens). The main role of these proteins is to ensure long-term survival of the parasite in the body of the host. The surface of the larvae is covered by coat made of some of those proteins, which increases the parasite's chances of survival. Other proteins secreted by Toxocara spp affect production of cytokines of the infected organism and parasite modulates the immune response to infection by that. Presence of the larvae results in inhibition of immune response based on Th1 cells and promotes Th2 immune response, during which levels of IgE and eosinophiles are elevated. Production of regulatory T lymphocytes is also stimulated. Key words Toxocara spp., toxocariasis, TES, immunomodulation, regulatory T lymphocytes, cytokines
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Brno brownfields by the Svitava river
Macháček, Tomáš ; Ležatka,, Lukáš (referee) ; Májek, Jan (advisor)
The theme of the diploma thesis „Brno brownfields by the Svitava River“ Is design of contemporary city structure in Brno Husovice. The theisis deals with the analysis of the current situation, definition of problems and opportunities in the location and the design, based on these researches. Studied area is located on the riverbank of the Svitava River and is defined by Provazníkova, Dukelská třída and Svitavské nábřeží streets. In these days there are mostly located brownfields of the previous industry parks, storage spaces and development of family houses. The design puts emphasis on the gentle merge with the urban structure of the old Husovice and focuses on using modern architectonic and urban approaches as well, for example on multifunctionality of buildings. The riverbank is revitalised and attractive features are designed here, like the footbridges conneting both river sides and sittable stairs. These designs provide space for leisure time and a water control during the floods as well. The traffic solution is concerned on the design of the new Nová Dukelská street, connecting formerly Zbrojovka industry park and Provazníkova street.
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