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Abstract: In the developed world, declining prevalence of parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Current treatments for these chronic inflammatory conditions have little to no effect on their prevalence and are referred to as “controllers” rather than cures. There has been limited success in therapeutically targeting allergic and autoimmune pathways, leaving an unmet need for development of effective anti-inflammatories. We discuss the benefit of hookworm infections and the parasite’s ability to condition the immune system to prevent allergic asthma and inflammatory bowel diseases. We then examine the immunomodulatory properties of selected hookworm-derived proteins in these two models of inflammation. While hookworm protein therapy has yet to be fully exploited, the identification of these proteins and the mechanisms by which they skew the immune system will provide new avenues for controlling and optimally reversing key pathological processes important in allergic and inflammatory bowel diseases. [Copyright &y& Elsevier]

Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA – hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products ( Ov ES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south-eastern Asia. [ABSTRACT FROM AUTHOR]

The tegument of Schistosoma mansoni plays an integral role in host–parasite interactions, particularly during the transition from the free-living cercariae to the intra-mammalian schistosomula stages. This developmental period is characterised by the transition from a trilaminate surface to a heptalaminate tegument that plays key roles in immune evasion, nutrition and excretion. Proteins exposed at the surface membranes of newly transformed schistosomula are therefore thought to be prime targets for the development of new vaccines and drugs for schistosomiasis. Using a combination of tegumental labelling and high-throughput quantitative proteomics, more than 450 proteins were identified on the apical membrane of S. mansoni schistosomula, of which 200 had significantly regulated expression profiles at different stages of schistosomula development in vitro, including glucose transporters, sterols, heat shock proteins, antioxidant enzymes and peptidases. Current vaccine antigens were identified on the apical membrane ( Sm -TSP-1, calpain) or sub-tegumental ( Sm -TSP-2, Sm 29) fractions of the schistosomula, displaying localisation patterns that, in some cases, differ from that in the adult stage fluke. This work provides the first known in-depth proteomic analysis of the surface-exposed proteins in the schistosomula tegument, and some of the proteins identified are clear targets for the generation of new vaccines and drugs against schistosomiasis. [ABSTRACT FROM AUTHOR]