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Human cytokine responses during natural and experimental exposure to parasitic helminth infection

หน่วยงาน Edinburgh Research Archive, United Kingdom

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ชื่อเรื่อง : Human cytokine responses during natural and experimental exposure to parasitic helminth infection
นักวิจัย : Bourke, Claire Deirdre
คำค้น : human , cytokine , helminth , parasite , immune response , Schistosoma haematobium , Trichuris suis , allergic rhinitis
หน่วยงาน : Edinburgh Research Archive, United Kingdom
ผู้ร่วมงาน : Mutapi, Francisca , Gray, David , Biotechnology and Biological Sciences Research Council (BBSRC)
ปีพิมพ์ : 2555
อ้างอิง : http://hdl.handle.net/1842/9434
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Bourke, C.D., Maizels, R.M. and Mutapi, F. (2010). Acquired immune heterogeneity and its sources in human helminth infection. Parasitology: 138 (2): 139-159 , Imai, N., Rujeni, N., Nausch, N., Bourke, C.D., Appleby, L.J., Cowan, G., Gwisai, R., Midzi, N., Cavanagh, D., Mduluza, T., Taylor, D. and Mutapi, F. (2011). Exposure, infection, systemic cytokine levels and antibody responses in young children concurrently exposed to schistosomiasis and malaria. Parasitology: 138 (12): 1519-1533 , Mutapi, F., Bourke, C.D., Harcus, Y., Midzi, N., Mduluza, T., Turner, C. M. and Maizels, R.M. (2011a). Differential recognition of Schistosoma haematobium adult worm antigens by the human antibodies IgA, IgE, IgG1 and IgG4. Parasite Immunology: 33 (3): 181-192. , Mutapi, F., Imai, N., Nausch, N., Bourke, C.D., Rujeni, N., Mitchell, K.M., Midzi, N., Woolhouse, M.E.J., Maizels, R.M. and Mduluza, T. (2011b). Schistosome infection intensity is inversely related to auto-reactive antibody levels. PLoS ONE: 6 (5): e19149 , Mutapi, F., Rujeni, N., Bourke, C.D., Mitchell, K.M., Appleby, L., Nausch, N., Midzi, N., Woolhouse, M.E.J., Maizels, R.M. and Mduluza, T. (2011c). Schistosoma haematobium treatment in 1-5 year old children: Safety and efficacy of the anti-helminthic drug praziquantel. PLoS Neglected Tropical Diseases: 5 (5): e1143
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Over one third of the human population is currently infected by one or more species of parasitic helminth, but the immune responses elicited by these infections remain poorly defined. Studies in helminth-exposed human populations and laboratory models suggest that helminth infection elicits a range of different effector cell types and that protective immunity and resistance to immune-mediated pathology depends on the balance between these responses. The aim of this thesis was to investigate how cytokines, the molecular mediators of the immune system, can be used to characterise human immune phenotype during natural and experimental helminth infection. Cytokines associated with innate inflammatory (TNFα, IL-6 and IL-9), Thl (IFNγ, IL-2 and IL-12p70), Th2 (IL-4, IL-5 and IL-13), Th17 (IL-17A, IL-21 and IL-23) and regulatory (IL-10 and TGFβ)immune phenotypes were analysed to provide the most comprehensive analysis of cytokine responses in human helminth infection conducted to-date. Using a multivariate statistical approach cytokines were analysed as combined immune profiles to reflect their complex interactions in vivo. In the first part of the study venous blood samples collected from a cross-sectional cohort of 284 Zimbabweans (age range: 3 -86 years) endemically-exposed to Schistosoma haematobium were cultured with antigens from different stages of the parasite's life-cycle(cercariae, adult worms and eggs) and the anti-schistosome vaccine candidate antigen glutathionine-S-transferase (GST). Cytokines responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). These assays were repeated 6 weeks after clearance of infection by anti-helminthic treatment. Parasitological and demographic characterisation of the cohort before, 6 weeks, 6 and 18 months after treatment allowed cytokine responses to be related to epidemiological patterns of infection before treatment and the risk of re-infection after treatment. The main findings of this study were:Cytokine responses to the antigens of S. haematobium cercariae are more proinflammatory than those elicited by adult worms and eggs prior to treatment, reflecting the distinct proteomes and exposure patterns of the 3 life-cycle stages Young children (5-10 years old) have a more regulatory and Th17-polarised cytokine response to S. haematobium antigens than older children and adults. These responses are significantly associated with schistosome infection intensity and may contribute to the development of resistance to schistosomiasis with age and exposure to infection Anti-helminthic treatment leads to a shift in S. haematobium cercariae, egg and GST specific cytokine responses towards a more pro-inflammatory phenotype The magnitude of change in S. haematobium-specific cytokine profiles after treatment is dependent on schistosome infection intensity at the time of treatment Individuals who remain un-infected up to 18 months after treatment to clear schistosome infection have a more pro-inflammatory and IL-21-polarised response to S. haematobium antigens 6 weeks after treatment than those who become re-infected, suggesting that post-treatment cytokine profiles promote resistance to re-infection. The second part of the study assayed systemic, parasite and allergen-specific cytokine responses in 45 adults with seasonally exacerbated allergy to grass pollen who were experimentally exposed to Trichuris suis. Cytokine responses in infected individuals were compared to those of 44 un-infected controls. This aspect of the study showed that: Exposure to T. suis promotes systemic and parasite-specific Th2 and regulatory cytokine responses, but does not alter cytokine responses to environmental allergens.

บรรณานุกรม :
Bourke, Claire Deirdre . (2555). Human cytokine responses during natural and experimental exposure to parasitic helminth infection.
    กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom .
Bourke, Claire Deirdre . 2555. "Human cytokine responses during natural and experimental exposure to parasitic helminth infection".
    กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom .
Bourke, Claire Deirdre . "Human cytokine responses during natural and experimental exposure to parasitic helminth infection."
    กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom , 2555. Print.
Bourke, Claire Deirdre . Human cytokine responses during natural and experimental exposure to parasitic helminth infection. กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom ; 2555.