Suppression of host Th1-type granulomatous inflammation by Taenia solium metacestodes is related to down-regulation of osteopontin gene expression |
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Authors: | Wang I-Chuang Fan Ping-Chin Lu Sen-Chi Fan Chia-Kwung Su Kua-Eyre |
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Institution: | Division of Parasitology, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen Ai Road, Taipei 100, Taiwan, ROC. |
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Abstract: | 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 2weeks. Osteopontin (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 ES products from these metacestodes led to a decrease in OPN, IFN-gamma and IL-12 expression, whereas co-culture with somatic proteins enhanced OPN expression by leukocytes. Addition of recombinant mouse OPN (rmOPN) counteracted the down-regulation of IL-12 and IFN-gamma mRNA expression, but not OPN mRNA expression, in leukocyte cultures. Furthermore, injection of rmOPN into the tissues surrounding implanted cysticerci enhanced inflammatory responses while a similar injection of an anti-rmOPN antibody reduced inflammation. These findings suggest that the suppression of host Th1-type granulomatous inflammation by ES products from T. solium metacestodes is related to down-regulation of OPN gene expression. |
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Keywords: | Taenia solium OPN Cysticercosis Th1-type responses IL-12 IFN-γ Granulomatous inflammation |
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