Modulation of dendritic cell responsiveness by excretory-secretory products of the model tapeworm

Authors: Emilia Vendelova 1    Justin Komguep Nono 2    Klaus Brehm 3    Manfred Lutz 4    Gabriela Hrckova 1   
1 Parazitologický ústav, Košice, Slovensko    2 University of Cape Town, Africa    3 2University of Wϋrzburg, Institute of Hygiene and Microbiology, Wϋrzburg, Germany    4 3University of Wϋrzburg, Institute of Virology and Immunobiology, Wϋrzburg, Germany   
Year: 2014
Section: Cellular metabolism, physiology, molecular biology and genetics
Abstract No.: 1115
ISBN: 978-80-970712-6-4

There is an increasing recognition that exposures to infectious agents evoke effects on the immune system in terms of decresed hyperactivity (allergy, autoimmunity). Currently, the new trend apperared and so to treat these "modern diseases" with a live worms. Such treatment brings along lot of side effects and there is an effort to try to identify active factors which can play a role in immunomodulation of host immune response. Cestode represent class of worms with significant immunosuppresive potential. They cause debilitating diseases in mammals (in their larval forms) due to long asymptomatic infections. Despite this fact their immunomodulatory effect is highly understudied as compared to other helminths (nematodes and trematodes). Since dendritic cells (DC) are critically involved in stimulation and modulation of the host immune response by helminths, we sought to reveal poorly understood influence of cestodes on these important cells using an in vitro stimulation systems and an in vivo model of intraperitoneal injection of the model cestode Mesocestoides vogae (syn. M. corti). Although considerably recruited to the site of infection, host DC failed to produce elevated amounts of IL-12p70 in M. vogae injected mice when compared to mock-injected controls. In vitro, we found that neither excreted/secreted (E/S) products nor somatic extracts of the parasite were able to induce conventional maturation of DC (as judged by MHC II class and CD86 surface marker expression and cytokine production). Moreover, whereas the parasite secretions significantly suppressed LPS-induced production of IL12p70, somatic extracts failed to do so. A bio-assay guided biochemical analysis of the parasite secreted product(s) revealed that the observed effect was most likely driven by a glycoprotein. Finally, an analysis of the protein profiles of parasite secreted (active) and somatic (inactive) antigens provided us with several differentially expressed proteins that could constitute efficient anti-inflammatory factors. The identification strategy of such factor(s) and the possible implication of our findings for cestode immunomodulation will be discussed.

The authors thank the Nadácia SPP hlavička, Národný štipendijný fond SR and Boeringer Ingelheim company (Germany.