Comparative serum metabolomics between SCID mice and BALB/c mice with or without Schistosoma japonicum infection: Clues to the abnormal growth and development of schistosome in SCID mice

Comparative serum metabolomics between SCID mice and BALB/c mice with or without Schistosoma japonicum infection: Clues to the abnormal growth and development of schistosome in SCID mice
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DOI:
10.1016/j.actatropica.2019.105186
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发表时间:
2019-12-01
期刊:
影响因子:
2.7
通讯作者:
Ming Zhenping
Ming Zhenping
中科院分区:
医学2区
文献类型:
--
作者:
Liu Rong;Ye Feng;Ming Zhenping

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血吸虫属血吸虫(Schistosoma)是引起人畜共患血吸虫病的主要寄生虫之一,其生长发育依赖于宿主的免疫相关因子,其虫卵沉积于宿主的肝脏和肠壁形成肉芽肿性病变。血吸虫发育在仅缺乏T细胞的小鼠中受阻,并且在缺乏T和B淋巴细胞的严重联合免疫缺陷(SCID)小鼠中甚至更严重地延迟。然而,宿主免疫系统对嗜水气单胞菌生长发育的潜在调控分子机制尚不清楚。因此,本研究检测并比较了免疫缺陷小鼠和免疫功能正常小鼠(SCID小鼠和BALB/c小鼠)在S.日本血吸虫感染(在感染后第35天,使用液相色谱-质谱(LC-MS))。共识别出正离子模式下的705个离子特征和负离子模式下的242个离子特征。首先,在SCID小鼠和没有S.日本血蠕虫感染第二,在S.日本血吸虫感染,其中包括由于物种差异和对S.日本血吸虫感染代谢途径分析显示,S.日本血吸虫感染与血吸虫生长发育迟缓有关。日本血吸虫在SCID小鼠中的表达。这些发现为揭示宿主系统代谢变化对血吸虫生长发育影响的分子机制提供了新线索。日本血吸虫病的蠕虫,也为开发抗寄生虫和血吸虫病的药物或疫苗提供了非常有前途的候选者。
The small blood flukes of genus Schistosoma, which cause one of the most prevalent and serious parasitic zoonosis schistosomiasis, are dependent on immune-related factors of their mammalian host to facilitate their growth and development, and the formation of granulomatous pathology caused by eggs deposited in host's liver and intestinal wall. Schistosome development is hampered in the mice lacking just T cells, and is even more heavily retarded in the severe combined immunodeficient (SCID) mice lacking both T and B lymphocytes. Nevertheless, it's still not clear about the underlying regulatory molecular mechanisms of schistosome growth and development by host's immune system. This study, therefore, detected and compared the serum metabolic profiles between the immunodeficient mice and immunocompetent mice (SCID mice vs. BALB/c mice) before and after S. japonicum infection (on the thirty-fifth day post infection using liquid chromatography-mass spectrometry (LC-MS). Totally, 705 ion features in electrospray ionization in positive-ion mode (ESI+) and 242 ion features in ESI- mode were identified, respectively. First, distinct serum metabolic profiles were identified between SCID mice and BALB/c mice without S. japonicum worms infection. Second, uniquely perturbed serum metabolites and their enriched pathways were also obtained between SCID mice and BALB/c mice after S. japonicum infection, which included differential metabolites due to both species differences and differential responses to S. japonicum infection. The metabolic pathways analysis revealed that arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and purine metabolism were enriched based on the differential serum metabolites between SCID mice and BALB/c mice after S. japonicum infection, which was addressed to be related to the retarded growth and development of S. japonicum in SCID mice. These findings provide new clues to the underlying molecular events of host's systemic metabolic changes on the growth and development of S. japonicum worms, and also provide quite promising candidates for exploitation of drugs or vaccines against schistosome and schistosomiasis.