A novel mouse model of Schistosoma haematobium egg-induced immunopathology.
A novel mouse model of Schistosoma haematobium egg-induced immunopathology.
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DOI：
10.1371/journal.ppat.1002605
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Hsieh MH
中科院分区：
文献类型：
--
作者：
Fu CL;Odegaard JI;Herbert DR;Hsieh MH
埃及血吸虫是泌尿生殖道血吸虫病的病原体，是全世界超过1.12亿人发病和死亡的主要原因。链球菌感染寄生虫在泌尿道内产卵导致多种免疫病理学后遗症，其驱动炎症、血尿、纤维化、膀胱功能障碍和对尿路上皮癌的易感性增加。虽然人类很容易患上泌尿生殖道血吸虫病，但由于缺乏易于实验的模型，极大地损害了我们对这种重要疾病的发病机制的理解。我们建立了一种改良的S.一种尿路血吸虫感染，概括了人类泌尿生殖道血吸虫病的几个方面。显微注射纯化的S.在将血蜱虫卵植入膀胱壁后，小鼠持续发展出富含巨噬细胞的肉芽肿，持续至少3个月，并通过尿液排出虫卵。重要的是，注射卵子的小鼠也会发生尿路纤维化、膀胱功能障碍和各种尿路上皮变化，这些变化在形态上让人联想到人类泌尿生殖道血吸虫病。正如我所料，S。在直接微环境、引流淋巴结和体循环中，由血吸虫卵诱导的免疫应答与2型显性炎症应答相关，其特征在于高水平的白细胞介素-4、嗜酸性粒细胞和IgE。总之，我们的新型小鼠模型可能有助于更好地理解与泌尿生殖道血吸虫病相关的上皮功能障碍，组织纤维化和肿瘤发生的独特病理生理机制。泌尿生殖道血吸虫病（感染寄生的埃及血吸虫，这是全球最常见的人类特有的血吸虫物种）影响着全世界超过1.12亿人。S.埃及血蠕虫主要在膀胱、上泌尿道和生殖道中产卵，宿主对这些卵的免疫反应被认为是引起这些器官中几乎所有相关疾病的原因。由此产生的症状包括血尿（血尿）、尿频、尿路纤维化（内部瘢痕）、膀胱癌风险增加以及感染HIV的易感性增强。每年约有15万人死于S。这种寄生虫仅由嗜血杆菌引起的阻塞性肾衰竭，使其成为世界上最致命的蠕虫之一。尽管S.然而，由于缺乏实验上可操作的模型，导致缺乏对这种寄生虫的研究。我们已经绕过了天然S的障碍。通过将寄生虫卵直接显微注射到膀胱壁中，在小鼠膀胱中进行血吸虫产卵。这会引发炎症、血尿、尿频、纤维化、虫卵脱落和上皮细胞改变，这些与临床上在S。嗜血杆菌感染我们的模型可能提供新的机会，更好地了解泌尿生殖道血吸虫病的基本分子和细胞免疫学，从而有助于新的诊断和治疗的发展。
Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis. Urogenital schistosomiasis (infection with parasitic Schistosoma haematobium worms, the most common human-specific Schistosoma species globally) affects over 112 million people worldwide. S. haematobium worms primarily lay eggs in the bladder, upper urinary and genital tracts, and the host immune response to these eggs is considered to cause almost all associated disease in these organs. Resulting conditions include hematuria (bloody urine), urinary frequency, fibrosis (internal scarring) of the urinary tract, increased risk of bladder cancer, and enhanced susceptibility to contracting HIV. Approximately 150,000 people die annually from S. haematobium-induced obstructive kidney failure alone, making this species one of the deadliest worms worldwide. Despite the importance of S. haematobium, a lack of an experimentally manipulable model has contributed to the paucity of research focusing on this parasite. We have circumvented the barriers to natural S. haematobium oviposition in the mouse bladder by directly microinjecting parasite eggs into the bladder wall. This triggers inflammation, hematuria, urinary frequency, fibrosis, egg shedding, and epithelial changes that are similar to that seen in clinical S. haematobium infections. Our model may provide new opportunities to better understand the basic molecular and cellular immunology of urogenital schistosomiasis and thereby contribute to the development of new diagnostics and therapeutics.
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影响因子：
3.1
作者：
Billips, Benjamin K.;Forrestal, Sarah G.;Schaeffer, Anthony J.
通讯作者：
Schaeffer, Anthony J.
DOI：
10.4269/ajtmh.1978.27.55
发表时间：
1978-01-01
影响因子：
3.3
作者：
CHEEVER, AW;ISMAIL;SIPPEL, JE
通讯作者：
SIPPEL, JE
影响因子：
3.5
作者：
ELTOUM, IA;GHALIB, HW;HOMEIDA, M
通讯作者：
HOMEIDA, M
影响因子：
2.1
作者：
BURDEN, CS;UBELAKER, JE
通讯作者：
UBELAKER, JE
DOI：
10.1080/00034983.1978.11719309
发表时间：
1978-01-01
影响因子：
--
作者：
GHANDOUR, AM
通讯作者：
GHANDOUR, AM