Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions

Vendelova, Emilia; De Lima, Jeferson Camargo; Lorenzatto, Karina Rodrigues; Monteiro, Karina Mariante; Mueller, Thomas; Veepaschit, Jyotishman; Grimm, Clemens; Brehm, Klaus; Hrčková, Gabriela; Lutz, Manfred B; Ferreira, Henrique B; Nono, Justin Komguep

Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions

Journal Article

2016

Journal Title

PLOS Neglected Tropical Diseases

Link to Journal

http://journals.plos.org/plosntds

Publisher

Public Library of Science

Publisher

University of Cape Town

Department

Institute of Infectious Disease and Molecular Medicine

Faculty

Faculty of Health Sciences

License

http://creativecommons.org/licenses/by/4.0

Abstract

Author Summary: The metacestode larval stages of life-threatening tapeworms grow within the organs of its mammalian hosts, thus causing severe and long-lasting morbidity. Immunosuppression, which mainly depends on factors that are released or leaking from the parasite, plays an important role in both survival and proliferation of the larvae. These parasite-derived molecules are potential targets for developing new anti-parasitic drugs and/or improving the effectiveness of current therapies. Moreover, an optimized use of such factors could help to minimize pathologies resulting from uncontrolled immune responses, like allergies and autoimmune diseases. The authors herein 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. Employing modern analytic proteomic tools combined with immunological bioassays, several cestode-derived candidate immunomodulators were identified. This is the first bioassay-guided comprehensive library of candidate immunomodulators from a tissue-dwelling cestode larva. This work validates the unmet value of the Mesocestoides corti system in characterizing the mechanisms of host immunomodulation by metacestodes and reveals the largest database of candidate metacestode-derived immunomodulators until date.