School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Acta Trop. 2019 Dec;200:105186. doi: 10.1016/j.actatropica.2019.105186. Epub 2019 Sep 19.
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.
日本血吸虫等小型血吸蝴属寄生虫会导致最普遍和最严重的寄生虫病之一——血吸虫病，它们依赖于宿主的免疫相关因素来促进其生长和发育，并形成由卵在宿主肝和肠壁沉积引起的肉芽肿性病变。在缺乏 T 细胞的小鼠中，血吸虫的发育受阻，在缺乏 T 和 B 淋巴细胞的严重联合免疫缺陷 (SCID) 小鼠中甚至更为严重。然而，宿主免疫系统对血吸虫生长和发育的调控分子机制仍不清楚。因此，本研究采用液相色谱-质谱联用技术（LC-MS）检测并比较了日本血吸虫感染前后免疫缺陷（SCID 小鼠）和免疫正常（BALB/c 小鼠）小鼠的血清代谢谱（感染后第 35 天）。共鉴定出电喷雾电离正模式（ESI+）下的 705 个离子特征和 ESI-模式下的 242 个离子特征。首先，在没有日本血吸虫感染的情况下，SCID 小鼠和 BALB/c 小鼠的血清代谢谱明显不同。其次，在日本血吸虫感染后，SCID 小鼠和 BALB/c 小鼠之间也获得了独特的血清代谢物及其富集途径，包括由于物种差异和对日本血吸虫感染的不同反应而产生的差异代谢物。代谢通路分析显示，日本血吸虫感染后 SCID 小鼠和 BALB/c 小鼠之间差异代谢物富集的通路主要有花生四烯酸代谢、不饱和脂肪酸的生物合成、亚油酸代谢、糖基磷脂酰肌醇（GPI）-锚生物合成、α-亚麻酸代谢、甘油磷酯代谢、鞘脂代谢和嘌呤代谢等，这些通路可能与 SCID 小鼠中日本血吸虫生长发育迟缓有关。这些发现为宿主对日本血吸虫生长发育的系统代谢变化的潜在分子事件提供了新的线索，也为开发抗血吸虫和血吸虫病的药物或疫苗提供了很有前景的候选物。
