Abstract
Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M. vogae). We demonstrate that ES products but not larval homogenates inhibit the stimuli-driven release of the pro-inflammatory, Th1-inducing cytokine IL-12p70 by murine bone marrow-derived dendritic cells (BMDCs). Within the ES fraction, we biochemically narrowed down the immunosuppressive activity to glycoproteins since active components were lipid-free, but sensitive to heat- and carbohydrate-treatment. Finally, using bioassay-guided chromatographic analyses assisted by comparative proteomics of active and inactive fractions of the ES products, we defined a comprehensive list of candidate proteins released by M. corti tetrathyridia as potential suppressors of DC functions. Our study provides a comprehensive library of somatic and ES products and highlight some candidate parasite factors that might drive the subversion of DC functions to facilitate the persistence of M. corti tetrathyridia in their hosts.
Highlights
Cestodes in general and the metacestode larval stages in particular are of major etiological importance for both human and domestic animal diseases
The authors demonstrate that larvae from a parasitic cestode release factors that sufficiently support the suppression of dendritic cells, a set of innate immune cells that recognizes and initiates host immune responses against invading pathogens
Further analyzing M. corti tetrathyridia ES products (McES) by bioassay-guided fractionation assisted with liquid chromatography-mass spectrometry, we identified a set of candidate proteins that might mediate M. corti tetrathyridia suppression of dendritic cells (DCs)
Summary
Cestodes in general and the metacestode larval stages in particular are of major etiological importance for both human and domestic animal diseases. Major life-threatening human cestodes such as T. solium, E. granulosus and E. multilocularis cause serious diseases due to the unique ability of their metacestode larvae to persist within the host tissues for decades, gradually impairing the function of the colonized organ [1,2]. Metacestodes dwell in the host tissues where they confront the immune system and modulate the immune response to enable their survival and the establishment of a chronic infection [3]. For tissuedwelling metacestodes, interference with IL-12 production by DC is critical for limiting proinflammatory Th1 immunity and allowing parasite persistence [2,5,6,7,8,9,10]. How metacestodes modulate DC functions is largely unclear [2]
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