Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic Nematodes Strongyloides ratti and Trichuris suis Affects Mucosal Homeostasis.

Dana Ditgen,Guido Schramm,Norbert W Brattig,Jan Hansmann,Dominic Winter,Klaus D Erttmann,Emmanuela M Anandarajah,Eva Liebau

doi:10.1155/2016/8421597

Abstract

The cellular redox state is important for the regulation of multiple functions and is essential for the maintenance of cellular homeostasis and antioxidant defense. In the excretory/secretory (E/S) products of Strongyloides ratti and Trichuris suis sequences for thioredoxin (Trx) and Trx-like protein (Trx-lp) were identified. To characterize the antioxidant Trx-lp and its interaction with the parasite's mucosal habitat, S. ratti and T. suis Trx-lps were cloned and recombinantly expressed. The primary antioxidative activity was assured by reduction of insulin and IgM. Further analysis applying an in vitro mucosal 3D-cell culture model revealed that the secreted Trx-lps were able to bind to monocytic and intestinal epithelial cells and induce the time-dependent release of cytokines such as TNF-α, IL-22, and TSLP. In addition, the redox proteins also possessed chemotactic activity for monocytic THP-1 cells and fostered epithelial wound healing activity. These results confirm that the parasite-secreted Trx-lps are multifunctional proteins that can affect the host intestinal mucosa.

Highlights

Parasitic intestinal nematodes are widespread, affecting human and vertebrates
SrTrx-lp is represented by the cluster SR00399 [13] and was abundantly found in S. ratti E/S products of parasitic S. ratti females
The partial sequence was identified as the thioredoxin family protein and was used to obtain the full-length cDNA sequence by PCR

Summary

Introduction

Parasitic intestinal nematodes are widespread, affecting human and vertebrates. Worldwide, more than one-third of mankind is infected with helminths [1] of which 100–200 million people are infected with Strongyloides [2, 3] and approximately 800 million with Trichuris [4]. The investigated nematodes Strongyloides ratti and Trichuris suis are very closely related to their human-pathogenic homologues Strongyloides stercoralis and Trichuris trichiura [5, 6]. In case of S. ratti and T. suis, these E/S products include antioxidative proteins such as thioredoxin (Trx), heat shock proteins, and numerous proteases as well as protease inhibitors, galectins, and orthologous of host cytokines [10, 12,13,14,15,16]. Trx has been reported in E/S products of multiple helminths [17,18,19,20]. These E/S proteins have been detected in extracellular vesicles from helminths [21]

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Conclusion