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

• Published in: Journal of Parasitology Research 2016, Vol.2016 (2016), p.193-209
• Main Authors: Brattig, Norbert, Erttmann, Klaus D., Schramm, Guido, Winter, Dominic, Hansmann, Jan, Anandarajah, Emmanuela M., Ditgen, Dana, Liebau, Eva
• Format: Article
• Language: English
• Subjects: Development and progression; Genetic aspects; Homeostasis; Physiological aspects; Strongyloidiasis; Thioredoxin
• ISSN: 2090-0023; 2090-0031
• DOI: 10.1155/2016/8421597

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.