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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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Signaling systems of TLR receptors in microglia
Prokop, Jonáš ; Novotný, Jiří (advisor) ; Filipp, Dominik (referee)
Emerging importance of TLR signalling in microglia has been suggested by various studies of neuroinflammation. Both MyD88 dependent and TRIF dependent pathways used by TLR induce secretion of proinflammatory cytokines in microglia by the activation of transcriptional factors such as NF-κB. This in turn polarizes the whole microglial population to a proinflammatory phenotype. Under physiological conditions microglia express various anti-inflammatory and growth factors and serve in the maintenance of the CNS. Once activated, microglia are connected to neuroinflammation and in the case of overactivation to neurodegeneration. Research of TLR signalling in microglial populations is important for our understanding of complex pathologies of the central nervous system. Moreover, exact knowledge of associated mechanisms might prove very useful in finding new therapeutic approaches. Key words: Microglia, signalling systems of toll-like receptors, Myd88, TRIF, neuroinflammation, neurodegeneration
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Production of cytokines in mice infected with bird schistosome Trichobilharzia regenti
Majer, Martin ; Macháček, Tomáš (advisor) ; Černý, Jan (referee)
The neuropathogenic trematode Trichobilharzia regenti (Schistosomatidae) infects the central nervous system of birds and mammals. During its migration through the spinal cord, the parasite causes tissue damage and triggers inflammation which is likely responsible for the elimination of the parasite. In this thesis, the proinflammatory cytokines IL-1β and IL-17 were detected by immunohistochemistry in the affected spinal cord of C57BL/6J mice during the infection. Additionally, IL-4 and IL-6, participating in the regulation of the inflammation and tissue repair, respectively, were noticed. Astrocytes, microglia and other, yet unidentified cells, produced these cytokines. Furthermore, splenic T-lymphocytes were phenotyped by flow cytometry to characterize peripheral immune response. At the peak of nervous tissue inflammation, mixed (Th1/Th2) cellular immune response was observed. Taken together, this thesis extended the knowledge of cytokine immune response of mice infected with T. regenti and also confirmed that inflammation in the nervous tissue influences the polarization of peripheral immune response. Key words: cytokines, spleen, CNS, microglia, astrocytes, Trichobilharzia regenti, immunohistochemistry, flow cytometry
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Glial cells and their role in amyotrophic lateral sclerosis
Vaňátko, Ondřej ; Anděrová, Miroslava (advisor) ; Černý, Jan (referee)
Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) is a progressive neurodegenerative disorder. It affects upper and lower motor neurons in the brain motor cortex, the brain stem and the spinal cord, causing their death, which results in denervation of voluntary muscles. Progressive muscle weakness and atrophy throughout the entire body gradually leads to worsening of the ability to move, speak, chew, swallow and eventually breath. Ultimately it results in affected individual's death due to respiratory muscle failure. Although first identified in 1869, no cure for ALS has been yet found. While early studies focused mainly on the research of motor neurons themselves, the attention has shifted towards glial cells in the past two decades. Glial cells are essential for proper neuron functioning and survival and it appears that they play a major role in ALS progression. The goal of this thesis is to review and summarize findings on the role of glial cells in ALS over the last years, focusing on four specific types of glial cells, namely astrocytes, microglia, oligodendrocytes and NG2-glia. Key words: amyotrophic lateral sclerosis, ALS, motor neuron, glia, astrocyte, microglia, oligodendrocyte, NG2-glia
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Changes in neuroglia in degenerative disorders of the central nervous system
Kirdajová, Denisa ; Zach, Petr (advisor) ; Hock, Miroslav (referee)
Neurodegenerative diseases are a serious disorders of the central nervous system characterized by neuronal loss with a subsequent damage of the brain. This damage may have diverse consequences like a gradual loss of memory and intellect, problems with musculoskeletal system and not least death. Causes of these diseases are not yet fully understood. In addition to neurons neuroglia also plays an important role in these diseases of the central nervous system. In neurodegenerative diseases are astrocytes, oligodendrocytes, microglia and NG2 cells involved in their many aspects. They participate in the protective as well as in the detrimental aspect of these diseases. This work, therefore, presents an overview of previously acquired knowledge of neuroglia in various types of degenerative disorders of the CNS (Alzheimer`s disease, Parkinson`s disease, amyotrophic lateral sclerosis, multiple sclerosis, Wernicke encephalopathy, HIV associated dementia, frontotemporal dementia, vascular dementia). Powered by TCPDF (www.tcpdf.org)
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Calcium signalling in glial cells in progress of Alzheimer disease
Waloschková, Eliška ; Anděrová, Miroslava (advisor) ; Maršáková, Lenka (referee)
Alzheimer's disease (AD) is a neurodegenerative disorder affecting the entire central nervous system including glial cells. The mechanisms of this disease are not yet entirely clear, although recent studies suggest that among the known hallmarks of AD, such as accumulation of amyloid β and hyperphosphorylated tau, dysregulation of intracellular calcium homeostasis is proposed to be a significant feature both in neurons and glial cells, namely astrocytes and microglia. Glial cells play an important role both in healthy brain and during AD progression. Their major functions, such as supporting neurons or maintaining synapses, are impaired during this disease. Recent findings suggest that aberrant glial calcium signaling activated during AD, could possibly promote the malfunction of these cells and increase their inflammatory response, thus affecting neurons and causing brain damage. It is likely, that the ongoing inflammation and the impaired calcium signaling affect one another, consequently enhancing the progression of AD.
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Nervous tissue regeneration following ischemic injury in adulthood - the role of glial cells
Kamenická, Monika ; Anděrová, Miroslava (advisor) ; Kletečková, Lenka (referee)
Ischemic stroke (ischemia) is one of the most common causes of death in the world. The consequences of this disease are enormous and markedly affect the lives of patients who often are unable to live a full quality of life as before. Therefore, the current research is focused on elucidating new mechanisms that could mitigate the effects of ischemia and better regeneration of nerve tissue. This theses aims to summarize the current knowledge about neurogenesis/gliogenesis in the nerve tissue under physiological conditions, after ischemic injury and subsequent regeneration. The first chapter is focused on neurogenesis in the nervous tissue of adults. The two main neurogenic regions are described, such as subventricular zone and the gyrus dentatus in hippocampus. The following is a brief description of cells that are located in neurogenic regions and their function under physiological conditions. The second chapter focuses on gliogenesis in adult nervous tissue and describes the glial cells responsible for numerous functions in CNS. Furthermore, the functions of individual types of glial cells are listed. The third chapter gives the overview about pathophysiology of ischemia. The author tries to explain what is happening in the brain tissue during and following ischemia, what types of ischemia are...
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Role of glial cells in the immune response of mice infected by neurotropic fluke Trichobilharzia regenti
Macháček, Tomáš ; Panská, Lucie (advisor) ; Kopecký, Jan (referee)
A central nervous system (CNS) can be invaded by plenty of parasites, including parasitic helminths. Host's immune response during such infections includes not only participation of peripheral lymphocytes, but also astrocytes and microglia, resident glial cells present in the CNS. Activation of astrocytes and microglia has been recently demonstrated also in mice infected by neurotropic avian trematode Trichobilharzia regenti (Digenea: Schistosomatidae) for which mammals represent accidental hosts. The parasite does not mature in them and elicits development of inflammatory reaction in the CNS which may take part in parasite's destruction. Employing in vitro experiments, this thesis aimed at evaluation of the possible role of astrocytes and microglia in murine immune response to T. regenti. For this purpose, primary astrocyte and microglia culture preparations were established and the cells were then stimulated by antigens of T. regenti (homogenate of transformed cercariae, recombinant cathepsins B1.1 and B2). After that, production of nitric oxide and proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) was measured. The results revealed that in vitro stimulated astrocytes and microglia increase production of nitric oxide, IL-6 and TNF-alpha. Such response to parasite's antigens could influence...
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