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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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Leishmania tropica: immunopathology and genetic control
Sohrabi, Yahya ; Lipoldová, Marie (advisor) ; Pravenec, Michal (referee) ; Sádlová, Jovana (referee)
Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis cause by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe and effective drug and vaccine against the L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infection in animals. The aims of the present project were development of a suitable mouse model of the infection caused by L. tropica, and the study of mechanisms of the disease, and also mapping controlling genes/loci. We analysed susceptibility to L. tropica infection using recombinant congenic (RC) CcS/Dem mouse strains. These strains differ greatly in susceptibility to L. major due to random distribution of 12.5% of STS...
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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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Leishmania tropica: immunopathology and genetic control
Sohrabi, Yahya ; Lipoldová, Marie (advisor) ; Pravenec, Michal (referee) ; Sádlová, Jovana (referee)
Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis cause by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe and effective drug and vaccine against the L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infection in animals. The aims of the present project were development of a suitable mouse model of the infection caused by L. tropica, and the study of mechanisms of the disease, and also mapping controlling genes/loci. We analysed susceptibility to L. tropica infection using recombinant congenic (RC) CcS/Dem mouse strains. These strains differ greatly in susceptibility to L. major due to random distribution of 12.5% of STS...
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