Modulation of Human T Cell Responses and Macrophage Functions by Onchocystatin, a Secreted Protein of the Filarial Nematode Onchocerca volvulus
Annett A. Schönemeyer,Richard Lucius,Bettina Sonnenburg,Norbert Brattig,Robert Sabat,Klaus Schilling,Janette E. Bradley,Susanne Hartmann +7 more
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TLDR
Recombinant onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.Abstract:
Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immune responses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-alpha. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.read more
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Immune regulation by helminth parasites: cellular and molecular mechanisms.
TL;DR: Long-lived parasites such as the helminths are more remarkable for their ability to downregulate host immunity, protecting themselves from elimination and minimizing severe pathology in the host.
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Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity
TL;DR: Current understanding of the growing number of individual helminth mediators that have been shown to target key receptors or pathways in the mammalian immune system is summarised.
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Proteases in parasitic diseases
TL;DR: This review focuses on the direct role of proteases in disease pathogenesis and well-characterized examples of the roles proteases play in pathogenesis include their involvement in invasion of the host by parasite migration through tissue barriers, degradation of hemoglobin and other blood proteins, immune evasion, and activation of inflammation.
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Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules.
TL;DR: The secreted molecules by which Parasitic helminths modulate the immune system, preventing immune‐mediated ejection and suppressing immune‐ mediated diseases are described and the methods by which these molecules have evolved are described.
Journal ArticleDOI
A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages.
Corinna Schnoeller,Sebastian Rausch,Smitha P. S. Pillai,Angela Avagyan,Bianca M. Wittig,Christoph Loddenkemper,Alf Hamann,Eckard Hamelmann,Richard Lucius,Susanne Hartmann +9 more
TL;DR: It is reported herein that filarial cystatin, a secreted protease inhibitor of filarial nematodes, suppresses Th2-related inflammation and the ensuing asthmatic disease in a murine model of OVA-induced allergic airway responsiveness.
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