Life Sciences Commons^™

Molecular Characterization Of A Tetraspanin From The Human Liver Fluke, Opisthorchis Viverrini, Supawadee Piratae, Smarn Tesana, Malcolm K. Jones, Paul J. Brindley, Alex Loukas, Erica Lovas, Veerachai Eursitthichai, Banchob Sripa, Sirikanda Thanasuwan, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood flukes where they are essential for tegument formation, are directly exposed to the immune system, …

Germline Transgenesis And Insertional Mutagenesis In Schistosoma Mansoni Mediated By Murine Leukemia Virus, Gabriel Rinaldi, Sabine E. Eckert, Isheng J. Tsai, Suttas Suttiprapa, Kristine J. Kines, Jose F. Tort, Victoria H. Mann, Daniel J. Turner, Matthew Berriman, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Functional studies will facilitate characterization of role and essentiality of newly available genome sequences of the human schistosomes, Schistosoma mansoni, S. japonicum and S. haematobium. To develop transgenesis as a functional approach for these pathogens, we previously demonstrated that pseudotyped murine leukemia virus (MLV) can transduce schistosomes leading to chromosomal integration of reporter transgenes and short hairpin RNA cassettes. Here we investigated vertical transmission of transgenes through the developmental cycle of S. mansoni after introducing transgenes into eggs. Although MLV infection of schistosome eggs from mouse livers was efficient in terms of snail infectivity, >10-fold higher transgene copy …

Gastrointestinal Cell Mediated Immunity And The Microsporidia, Magali M. Moretto, Imtiaz A. Khan, Louis M. Weiss

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Vasa-Like Dead-Box Rna Helicases Of Schistosoma Mansoni, Danielle E. Skinner, Gabriel Rinaldi, Sutas Suttiprapa, Victoria H. Mann, Pablo Smircich, Alexis A. Cogswell, David L. Williams, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of …

Elevated Plasma Il-6 Associates With Increased Risk Of Advanced Fibrosis And Cholangiocarcinoma In Individuals Infected By Opisthorchis Viverrini, Banchob Sripa, Bandit Thinkhamrop, Eimorn Mairiang, Thewarach Laha, Sasithorn Kaewkes, Paiboon Sithithaworn, Maria V. Periago, Vajarabhongsa Bhudhisawasdi, Ponlapat Yonglitthipagon, Jason Mulvenna, Paul J. Brindley, Alex Loukas, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and …

Five-Year Longitudinal Assessment Of The Downstream Impact On Schistosomiasis Transmission Following Closure Of The Three Gorges Dam., Darren J. Gray, Aaron P. Thrift, Gail M. Williams, Feng Zheng, Yue-Sheng Li, Jiagang Guo, Honggen Chen, Tianping Wang, Xin J. Xu, Rong Zhu, Hongqing Zhu, Chun Li Cao, Dan D. Lin, Zhen Y. Zhao, Robert S. Li, George M. Davis, Donald P. Mcmanus

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes.

Methodology/Principal Findings

We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission …

Enhanced Protective Efficacy Of A Chimeric Form Of The Schistosomiasis Vaccine Antigen Sm-Tsp-2, Mark S. Pearson, Darren A. Pickering, Henry J. Mcsorley, Jeffrey M. Bethony, Leon Tribolet, Annette M. Dougall, Peter J. Hotez, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoniendemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to …

Characterising The Mucosal And Systemic Immune Responses To Experimental Human Hookworm Infection., Soraya Gaze, Henry J. Mcsorley, James Daveson, Di Jones, Jeffrey M. Bethony, Luciana M. Oliveira, Richard Speare, James S. Mccarthy, Christian R. Engwerda, John Croese, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after …

Redefining Chronic Toxoplasmosis: A T Cell Exhaustion Perspective, Rajarshi Bhadra, Imtiaz A. Khan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Cell-Free Circulating Mirna Biomarkers In Cancer., Meng-Hsuan Mo, Liang Chen, Yebo Fu, Wendy Wang, Sidney W. Fu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA) is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally …