Suppression of host Th1-type granulomatous inflammation by Taenia solium metacestodes is related to down-regulation of osteopontin gene expression.
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.
Wang
I-Chuang
IC
Division of Parasitology, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen Ai Road, Taipei 100, Taiwan, ROC.
Fan
Ping-Chin
PC
Lu
Sen-Chi
SC
Fan
Chia-Kwung
CK
Su
Kua-Eyre
KE
D000818:Animals; D003552:Cysticercus / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D041201:Taenia solium / Q000502:physiology*; D013622:Taeniasis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D053495:Osteopontin; D018664:Interleukin-12; D007371:Interferon-gamma