Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development.

Abstract

To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4⁺ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica.

• Authors: Hong You, Chang Liu, Xiaofeng Du, Sujeevi Nawaratna, Vanessa Rivera, Marina Harvie, Malcolm Jones, Donald P McManus
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 8 (Aug 16 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30115897 (Publication Type: Journal Article)

Chemical References

• Cytokines
• RNA, Double-Stranded
• RNA, Messenger
• Receptors, Nicotinic
• Vaccines
• Acetylcholinesterase
• Glucose

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Antibody Formation
• Cytokines (metabolism)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Glucose (metabolism)
• Liver (parasitology, pathology)
• Mice, Inbred CBA
• Ovum (metabolism)
• Parasites (enzymology, genetics, growth & development)
• RNA Interference
• RNA, Double-Stranded (metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, Nicotinic (genetics, metabolism)
• Schistosoma japonicum (enzymology, genetics, growth & development)
• Schistosomiasis japonica (immunology, parasitology)
• Spleen (metabolism)
• Transcription, Genetic
• Treatment Outcome
• Vaccination
• Vaccines (immunology)