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

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.

Quantitative multiplexed proteomics of Taenia solium cysts obtained from the skeletal muscle and central nervous system of pigs

“…These protein patterns could represent a homeostatic adaptation to the biochemical conditions in different tissue environments (SM vs CNS). Our dataset was compared with others previous proteomic reports for helminths [ 26 – 28 ; 59 ]. From our dataset, 167 proteins were considered excretion/secretion proteins (compared with the T .…”

“…We compared our proteomic dataset with several comprehensive proteomic studies performed in Echinococcus granulosus [ 26 ], E . multilocularis [ 27 ], Mesocestoides corti [ 28 ] and the theoretical secretome of T . solium [ 59 ].…”

The secreted protein signature of hydatid fluid from pulmonary cystic echinococcosis

“…Molecular characterization of the HF content is essential for a better understanding of the infection caused by Echinococcus spp., as well as for the discovery of new molecules with potential use in cystic echinococcosis diagnosis and treatment. Proteomic studies of helminth ES products have been particularly valuable for the identification of proteins involved in host-parasite relationship [10][11][12]. Prior Echinococcus spp.…”

Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha

“…The immune response to schistosomiasis, similarly to that against other tissue-dwelling helminth infections [ 4 – 6 ], is highly polarized as it progresses, going from i) an early Th1 response to ii) a powerful Th2 response that culminates as the adult parasite-released eggs are trapped in the host tissues [ 2 , 3 ] and finally iii) a chronic regulatory phase with a minimized but still dominant Th2 response [ 3 , 7 , 8 ] with a more clinically relevant tissue fibroproliferative pathology. Our current understanding of schistosomiasis pathology heavily relies on the use of experimental murine models [ 2 ].…”