Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential

• Authors: Hong You, QIMR Berghofer Medical Research Institute; Geoffrey Gobert, QIMR Berghofer Medical Research Institute; Pengfei Cai, QIMR Berghofer Medical Research Institute; Rong Mou, Guiyang Medical University; Sujeevi Nawaratna, QIMR Berghofer Medical Research Institute; Guofu Fang, Emory University; Francois Villinger, Emory University; Donald P. McManus, QIMR Berghofer Medical Research Institute
• Journal Title: PLoS Neglected Tropical Diseases
• Volume: Volume 9, Number 5
• Publisher: Public Library of Science | 2015-05-11, Pages e0003730-e0003730
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pntd.0003730
• Subjects: Biology, Parasitology; Health Sciences, Pathology; Biology, Physiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Infectious Diseases; Parasitology; Tropical Medicine; REPUBLIC-OF-CHINA; GLUCOSE-TRANSPORT; MANSONI; TRANSMISSION; PRAZIQUANTEL; PROTECTION; INFECTION; PATHWAYS; REVEALS; KINASE

Abstract

To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines.