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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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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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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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Critical factors affecting pathogen development in sand flies
Jančářová, Magdaléna ; Volf, Petr (advisor) ; Ratinier, Maxime (referee) ; Bilej, Martin (referee)
This thesis deals with barriers and factors critical for development of viruses, leishmania and gregarines in sand flies. First, we focused on life cycle of sand fly-borne phleboviruses, especially possible routes of sand fly infection. As a laboratory model we chose Massilia virus (MASV), species closely related to Toscana virus, which is main causative agent of summer meningitis in Mediterranean area. We tested different ways of infection by MASV in various developmental stages of Phlebotomus perniciosus; infection of (i) first (L1) and fourth (L4) instar larvae through larval food, (ii) females by blood meal, (iii) both sexes by sugar meal. Infection of L1 and L4 by larval food and subsequent transstadial MASV transmission to adults were not efficient; from 875 adults only three were MASV-positive. Infection through bloodmeal led to high infection rate before defecation, nevertheless, post defecation the infection rate declined and only 5 out of 27 females were MASV-positive. The most efficient infection way was through the sugar meal: 72% of females (88 out of 122) and 51% of males (58 out of 113) were detected as MASV-positive. Moreover, both males and females infected by this way released MASV particles into the drop of sugar which stayed infectious for next 24 hours for other naïve sand...
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Critical factors affecting pathogen development in sand flies
Jančářová, Magdaléna
This thesis deals with barriers and factors critical for development of viruses, leishmania and gregarines in sand flies. First, we focused on life cycle of sand fly-borne phleboviruses, especially possible routes of sand fly infection. As a laboratory model we chose Massilia virus (MASV), species closely related to Toscana virus, which is main causative agent of summer meningitis in Mediterranean area. We tested different ways of infection by MASV in various developmental stages of Phlebotomus perniciosus; infection of (i) first (L1) and fourth (L4) instar larvae through larval food, (ii) females by blood meal, (iii) both sexes by sugar meal. Infection of L1 and L4 by larval food and subsequent transstadial MASV transmission to adults were not efficient; from 875 adults only three were MASV-positive. Infection through bloodmeal led to high infection rate before defecation, nevertheless, post defecation the infection rate declined and only 5 out of 27 females were MASV-positive. The most efficient infection way was through the sugar meal: 72% of females (88 out of 122) and 51% of males (58 out of 113) were detected as MASV-positive. Moreover, both males and females infected by this way released MASV particles into the drop of sugar which stayed infectious for next 24 hours for other naïve sand...
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Salivary proteins of sand flies and the immune aspects of Leishmania transmission
Kindlová, Michaela
Sand flies serve as the vectors of leishmaniasis and their saliva was shown to affect the outcome of Leishmania infection by immunomodulation of the host. On the other hand, sand fly saliva contains a large scale of farmacologically active proteins that are strongly immunogenous for bitten hosts and specific anti-saliva immunity initiated by repeated sand fly feeding provides protection against Leishmania infection. Specific cell-mediated immunity was shown to be the core of the protectivity; however, our data suggests that the protective immunity has certain limitations. In mice bitten by sand flies for prolonged periods, we observed the desenzitization in term of abrogation of the protective immunity. Thus, we can speculate that the protective effect of immunity is linked solely with the short-term exposure. Nevertheless, our experiments showed that this aspect is also conditioned by the immediate infection after the protective short-term immunization. Taken together, it seems that these limitations may explain the circulation of leishmaniasis in endemic areas, even though humans and animals are frequently immunized by bites of uninfected sand flies. Repeated sand fly feeding on various hosts also promotes production of anti-saliva antibodies that reflect the intensity of exposure. We...
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Critical factors affecting pathogen development in sand flies
Jančářová, Magdaléna
This thesis deals with barriers and factors critical for development of viruses, leishmania and gregarines in sand flies. First, we focused on life cycle of sand fly-borne phleboviruses, especially possible routes of sand fly infection. As a laboratory model we chose Massilia virus (MASV), species closely related to Toscana virus, which is main causative agent of summer meningitis in Mediterranean area. We tested different ways of infection by MASV in various developmental stages of Phlebotomus perniciosus; infection of (i) first (L1) and fourth (L4) instar larvae through larval food, (ii) females by blood meal, (iii) both sexes by sugar meal. Infection of L1 and L4 by larval food and subsequent transstadial MASV transmission to adults were not efficient; from 875 adults only three were MASV-positive. Infection through bloodmeal led to high infection rate before defecation, nevertheless, post defecation the infection rate declined and only 5 out of 27 females were MASV-positive. The most efficient infection way was through the sugar meal: 72% of females (88 out of 122) and 51% of males (58 out of 113) were detected as MASV-positive. Moreover, both males and females infected by this way released MASV particles into the drop of sugar which stayed infectious for next 24 hours for other naïve sand...
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Critical factors affecting pathogen development in sand flies
Jančářová, Magdaléna ; Volf, Petr (advisor) ; Ratinier, Maxime (referee) ; Bilej, Martin (referee)
This thesis deals with barriers and factors critical for development of viruses, leishmania and gregarines in sand flies. First, we focused on life cycle of sand fly-borne phleboviruses, especially possible routes of sand fly infection. As a laboratory model we chose Massilia virus (MASV), species closely related to Toscana virus, which is main causative agent of summer meningitis in Mediterranean area. We tested different ways of infection by MASV in various developmental stages of Phlebotomus perniciosus; infection of (i) first (L1) and fourth (L4) instar larvae through larval food, (ii) females by blood meal, (iii) both sexes by sugar meal. Infection of L1 and L4 by larval food and subsequent transstadial MASV transmission to adults were not efficient; from 875 adults only three were MASV-positive. Infection through bloodmeal led to high infection rate before defecation, nevertheless, post defecation the infection rate declined and only 5 out of 27 females were MASV-positive. The most efficient infection way was through the sugar meal: 72% of females (88 out of 122) and 51% of males (58 out of 113) were detected as MASV-positive. Moreover, both males and females infected by this way released MASV particles into the drop of sugar which stayed infectious for next 24 hours for other naïve sand...
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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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A comparison of the peritrophic matrix in four sand fly species (Diptera: Psychodidae) and its role in the Leishmania development (Kinetoplastida: Trypanosomatidae).
Homola, Miroslav ; Sádlová, Jovana (advisor) ; Hypša, Václav (referee)
anglický Phlebotomine sand flies (Diptera: Psychodidae) are the only proven vectors of Leishmania parasites (Kinetoplastida: Trypanosomatidae). In Nematoceran Diptera, including sand flies, adults produce a type 1 peritrophic matrix (PM) which is secreted in response to the distension of the midgut caused by blood meal. The PM is an acellular envelope composed of chitin fibres and proteins, which protects the midgut epithelium against abrasion and pathogens and improves digestion. In hematophagous insects, the PM also plays a central role in heme detoxification. Female sand flies acquire Leishmania with a bloodmeal and the parasites undergo complicated development in their gut finished by the colonization of the stomodeal valve. The PM is one of the most important barriers in Leishmania development and its role in the vector competence of the S. schwetzi is the main topic of this master thesis. The PM's kinetic and morfology in the S. schwetzi is compared with other three sand fly species which differ in susceptibility to L. donovani. The key role of the PM in S. schwetzi vector competence is finally proved by disrupting the PM using the exogenous chitinase from Beauveria bassiana. Under these artificial conditions, the Leishmania parasites (L. donovani and L. major) are able to exit the PM,...
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