Immunopathogenesis and diagnostics of Sarcocystis calchasi in pigeons

鸽子卡尔卡氏肉孢子虫的免疫发病机制和诊断

• 批准号: 212404166
• 负责人: Professor Dr. Achim Dieter Gruber, Ph.D.
• 金额: --
• 依托单位: Institut für Tierpathologie (WE12)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/212404166?language=en
• 关键词: Immunopathogenesis; diagnostics; Sarcocystis; calchasi; pigeons

Sarcocystis calchasi is the cause of pigeon protozoal encephalitis (PPE), a severe neurological disease in pigeons. Further intermediate hosts are psittacines and presumably woodpeckers. In recent years, several severe outbreaks of the disease have been reported world-wide. In the previous DFG-funded project “Epidemiology, host spectrum and diagnostics of a novel Sarcocystis species in pigeons”, its occurrence was detected at a high prevalence (27.8%) in racing pigeon lofts all over Germany. Inflammatory brain lesions without the presence of the pathogen are typical of PPE. The causal pathomechanism is currently not understood and could serve as a model for other encephalitides with unknown aetiologies. A dual immune modulation may be a unique feature of S. calchasi with an immune evasion in the early, schizogonic phase, and an induction of autoimmunity in the late phase of encephalitis. The diagnosis of PPE in live pigeons and parrots is currently only possible by testing a muscle biopsy. The proposed project aims to identify mechanisms of immune evasion and to test the trigger mechanism of S. calchasi-induced encephalitis. A pathway analysis in the pigeon will be conducted to identify possible manipulations by the parasite. As possible triggers of the encephalitis, two alternative hypotheses of a hit-and-run mechanism versus an immune-mediated disease will be tested. Future projects to characterise the molecular pathomechanisms may build on these results. A strong focus of the project is the identification of relevant surface proteins and other proteins that may be associated with the complex parasite-host interaction. The results are expected to widely deepen the understanding of the immunopathogenesis of PPE.The development of a serum-ELISA specific for S. calchasi aims to replace the invasive testing via muscle biopsy. As test antigens, previously identified proteins will be recombinantly synthesised. Detection of antibodies will lead to a better understanding of the host immune-reaction to S. calchasi and possibly the role of antibody development in the immunopathogenesis. Furthermore, the German-wide prevalence of S. calchasi antibodies in pigeons will be determined.Finally, we will address whether S. calchasi uses a broader spectrum of intermediate hosts. To this end, the occurrence of S. calchasi will be tested in further prey species of the final hosts, the goshawk and sparrowhawk.Overall, all aspects of the proposed project will aid in the understanding and better control of this new, widespread and important disease which also possesses potential importance for modelling other neurological diseases with complex immunopathomechanisms.

卡查肉孢子虫是鸽子原虫脑炎（PPE）的病因，这是一种鸽子严重的神经系统疾病。其他的中间宿主是鹦鹉，可能是啄木鸟。近年来，世界各地报告了几起严重的该病暴发。在之前DFG资助的项目“鸽子中一种新型肉孢子虫的流行病学、宿主谱和诊断”中，在整个德国的赛鸽鸽舍中检测到其发生率很高（27.8%）。没有病原体存在的炎性脑损伤是PPE的典型表现。因果病理机制目前还不清楚，可以作为其他脑炎与未知病因的模型。双重免疫调节可能是S. calchasi与免疫逃避在早期，免疫原性阶段，并诱导自身免疫性脑炎的晚期阶段。在活鸽子和鹦鹉中PPE的诊断目前只能通过测试肌肉活检。该项目旨在确定免疫逃避机制，并测试S。钙中毒引起的脑炎将在鸽子中进行途径分析，以确定寄生虫可能的操纵。作为脑炎的可能触发因素，将测试打了就跑机制与免疫介导的疾病的两种替代假设。未来的项目，以阐明分子病理机制可能建立在这些结果。该项目的一个重点是鉴定相关的表面蛋白和其他可能与复杂的寄生虫-宿主相互作用相关的蛋白。本研究的结果有望广泛加深对PPE免疫发病机制的认识。calchasi旨在通过肌肉活检取代侵入性测试。作为测试抗原，将重组合成先前鉴定的蛋白质。抗体的检测将导致更好地了解宿主对S. calchasi和可能的作用，抗体发展的免疫发病机制。此外，全德国流行的S。最后，我们将讨论是否S. calchasi使用更广泛的中间宿主。为此，S. calchasi将在最终宿主的其他猎物物种（苍鹰和雀鹰）中进行测试。总体而言，拟议项目的所有方面将有助于理解和更好地控制这种新的、广泛的和重要的疾病，这种疾病对模拟具有复杂免疫病理机制的其他神经系统疾病也具有潜在的重要性。