Article first published online: 8 JUN 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 1, pages 285–295, July 2011
How to Cite
Nair, S. S., Bommana, A., Bethony, J. M., Lyon, A. J., Ohshiro, K., Pakala, S. B., Rinaldi, G., Keegan, B., Suttiprapa, S., Periago, M. V., Hotez, P. J., Brindley, P. J. and Kumar, R. (2011), The metastasis-associated protein-1 gene encodes a host permissive factor for schistosomiasis, a leading global cause of inflammation and cancer. Hepatology, 54: 285–295. doi: 10.1002/hep.24354
Potential conflict of interest: Nothing to report.
Grant support from the National Center for Research Resources S10RR025565 was provided to the institutional imaging core facility for imaging studies. This work was supported in part by National Institutes of Health Grants CA98823 and CA98823-S1 and institutional new program funds (to R.K.).
- Issue published online: 24 JUN 2011
- Article first published online: 8 JUN 2011
- Accepted manuscript online: 12 APR 2011 08:17AM EST
- Manuscript Accepted: 3 APR 2011
- Manuscript Received: 3 MAR 2011
Schistosoma haematobium is responsible for two-thirds of the world's 200 million to 400 million cases of human schistosomiasis. It is a group 1 carcinogen and a leading cause of bladder cancer that occurs after years of chronic inflammation, fibrosis, and hyperproliferation in the host liver. The coevolution of blood flukes of the genus Schistosoma and their human hosts is paradigmatic of long-term parasite development, survival, and maintenance in mammals. However, the contribution of host genes, especially those discrete from the immune system, necessary for parasite establishment and development remains poorly understood. This study investigated the role of metastasis-associated protein-1 gene (Mta1) product in the survival of S. haematobium and productive infection in the host. Using a Mta−1 null mouse model, here we provide genetic evidence to suggest that MTA1 expression positively influences survival and/or maturation of schistosomes in the host to patency, as we reproducibly recovered significantly fewer S. haematobium worms and eggs from Mta1−/− mice than wild−type mice. In addition, we found a distinct loss of cytokine interdependence and aberrant Th1 and Th2 cytokine responses in the Mta1−/− mice compared to age-matched wild-type mice. Thus, utilizing this Mta1-null mouse model, we identified a distinct contribution of the mammalian MTA1 in establishing a productive host–parasite interaction and thus revealed a host factor critical for the optimal survival of schistosomes and successful parasitism. Moreover, MTA1 appears to play a significant role in driving inflammatory responses to schistosome egg–induced hepatic granulomata reactions, and thus offers a survival cue for parasitism as well as an obligatory contribution of liver in schistosomiasis. Conclusion: These findings raise the possibility to develop intervention strategies targeting MTA1 to reduce the global burden of schistosomiasis, inflammation, and neoplasia. (HEPATOLOGY 2011;)