School of Veterinary Science, The University of Queensland, Brisbane, QLD, Australia.
Medical Biological Centre, Queen's University Belfast, Belfast, UK.
Parasit Vectors. 2019 Apr 16;12(1):173. doi: 10.1186/s13071-019-3403-1.
Schistosome parasites lay up to a thousand eggs per day inside the veins of their mammalian hosts. The immature eggs deposited by females against endothelia of venules will embryonate within days. Approximately 30% of the eggs will migrate to the lumen of the intestine to continue the parasite life-cycle. Many eggs, however, are trapped in the liver and intestine causing the main pathology associated with schistosomiasis mansoni and japonica, the liver granulomatous response. Excretory-secretory egg proteins drive much of egg-induced pathogenesis of schistosomiasis mansoni, and Schistosoma japonicum induce a markedly distinct granulomatous response to that of S. mansoni.
To explore the basis of variations in this responsiveness, we investigated the proteome of eggs of S. japonicum. Using mass spectrometry qualitative and quantitative (SWATH) analyses, we describe the protein composition of S. japonicum eggs secretory proteins (ESP), and the differential expression of proteins by fully mature and immature eggs, isolated from faeces and ex vivo adults.
Of 957 egg-related proteins identified, 95 were exclusively found in S. japonicum ESP which imply that they are accessible to host immune system effector elements. An in-silico analysis implies that ESP are able of stimulating the innate and adaptive immune system through several different pathways. While quantitative SWATH analysis revealed 124 proteins that are differentially expressed by mature and immature S. japonicum eggs, illuminating some important aspects of eggs biology and infection, we also show that mature eggs are more likely than immature eggs to stimulate host immune responses.
Here we present a list of potential targets that can be used to develop better strategies to avoid severe morbidity during S. japonicum infection, as well as improving diagnosis, treatment and control of schistosomiasis japonica.
血吸虫寄生虫每天在其哺乳动物宿主的静脉中产卵多达一千枚。雌性虫体在小静脉内皮上沉积的未成熟卵在数天内会胚胎发育。大约 30%的卵会迁移到肠道腔中继续寄生虫的生命周期。然而,许多卵会被困在肝脏和肠道中,导致与曼氏血吸虫病和日本血吸虫病相关的主要病理学,即肝脏肉芽肿反应。排泄-分泌卵蛋白驱动了曼氏血吸虫病中许多卵诱导的发病机制,而日本血吸虫诱导的肉芽肿反应与曼氏血吸虫明显不同。
为了探究这种反应性变化的基础,我们研究了日本血吸虫卵的蛋白质组。使用质谱定性和定量(SWATH)分析,我们描述了日本血吸虫卵分泌蛋白(ESP)的蛋白质组成,以及从粪便和离体成虫中分离的完全成熟和未成熟卵中蛋白质的差异表达。
在鉴定的 957 种与卵相关的蛋白质中,有 95 种仅在日本血吸虫 ESP 中发现,这意味着它们可被宿主免疫系统效应元件识别。计算机分析表明,ESP 能够通过几种不同的途径刺激先天和适应性免疫系统。虽然定量 SWATH 分析揭示了 124 种成熟和未成熟日本血吸虫卵中差异表达的蛋白质,阐明了卵生物学和感染的一些重要方面,但我们也表明成熟卵比未成熟卵更有可能刺激宿主免疫反应。
在这里,我们提出了一份潜在靶标的清单,可用于开发更好的策略来避免日本血吸虫感染期间的严重发病,以及改善日本血吸虫病的诊断、治疗和控制。