The establishment of an animal model for cysticercosis and studies on down-regulation of Th1-type granulomatous inflammation by metacestodes of Taenia solium

• Main Authors: I-Chuang Wang, 王以莊
• Other Authors: Kua-Eyre Su
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/70586548424638576297

博士 === 臺灣大學 === 微生物學研究所 === 96 === In this study, we tried to use three inbred mice stains, C3H/HeN, C57BL/6 and BALB/cAnN established an animal model of Taenia solium and T. saginata asiatica metacestode infection for human cysticercosis. Worm recovery results demonstrated that C3H/HeN and C57BL/6 strains were able to be infected by injection of oncospheres. Moreover, C3H strain mice exhibited higher worm recovery than C57 mice. Immune response of mice was trended to Th2-type from 4 to 6 weeks post-infection, because the increase in total serum IgG1 level of C3H mice. Microarray analysis of C3H mice tissue surrounding 6-weeks-old viable T. solium cysticerci and tissue at similar location without cysticercus revealed that metacestodes infection led to the decrease in expression of inflammation- and Th1-type response related cytokines, and enhanced anti-inflammatory factors and Th2-type response cytokine expression. Of special interest was the drastic down-regulation in the expression of Osteopontin (OPN) gene. Furthermore, inflammation and granuloma formation in human neurocysticercosis has been attributed to Th1-type immune responses of the host. In the present murine model, over 94% of Taenia solium metacestodes were viable and elicited no granulomatous inflammation whereas parasites killed by praziquantel treatment elicited rapid granuloma formation that calcified within two weeks. OPN is a Th1-related cytokine that is up-stream of IL-12 and which may play an essential role in granuloma formation and calcification. OPN mRNA expression was down-regulated in tissues surrounding viable cysticerci, but was up-regulated in inflammatory tissues surrounding degenerating cysticerci. Moreover, co-culture with a viable cysticercus or excretory/secretory (ES) products from these metacestodes led to a decrease in OPN, IFN-γ, and IL-12 expression whereas co-culture with somatic protein enhanced OPN expression by leukocytes. Addition of recombinant mouse OPN (rmOPN) was able to counteract the down-regulation of IL-12 and IFN-γ mRNA expression, but not OPN mRNA expression in leukocyte cultures. Furthermore, injection of rmOPN into the tissues surrounding implanted cysticerci enhanced inflammatory responses while similar injection of anti-rmOPN antibody reduced inflammation. Suppression of host Th1-type granulomatous inflammation by ES products from T. solium metacestodes is related to down-regulation of OPN gene expression, confirming that OPN plays an important role in inflammation and granuloma formation. In conclusion, metacestodes inhibit Th1-type inflammation via decreasing expression of OPN gene and utilize this mechanism to escape damages caused by host immune response.