Nitric oxide blocks the development of the human parasite Schistosoma japonicum

Shen, J; Lai, D-H; Wilson, RA; Chen, Y-F; Wang, L-F; Yu, Z-L; Li, M-Y; He, P; Hide, G; Sun, X; Yang, T-B; Wu, Z-D; Ayala, FJ; Lun, Z-R

Abstract

Human schistosomiasis, caused by Schistosoma species, is a major public health problem affecting more than 700 million people in 78 countries, with over 40 mammalian host reservoir species complicating the transmission ecosystem. The primary cause of morbidity is considered to be granulomas induced by fertilized eggs of schistosomes in the liver and intestines. Some host species, like rats (Rattus norvegicus), are naturally intolerant to Schistosoma japonicum infection, and do not produce granulomas or pose a threat to transmission, while others, like mice and hamsters, are highly susceptible. The reasons behind these differences are still a mystery. Using inducible nitric oxide synthase knockout (iNOS−/−) Sprague–Dawley rats, we found that inherent high expression levels of iNOS in wild-type (WT) rats play an important role in blocking growth, reproductive organ formation, and egg development in S. japonicum, resulting in production of nonfertilized eggs. Granuloma formation, induced by fertilized eggs in the liver, was considerably exacerbated in the iNOS−/− rats compared with the WT rats. This inhibition by nitric oxide acts by affecting mitochondrial respiration and energy production in the parasite. Our work not only elucidates the innate mechanism that blocks the development and production of fertilized eggs in S. japonicum but also offers insights into a better understanding of host–parasite interactions and drug development strategies against schistosomiasis.

Citation

Shen, J., Lai, D.-H., Wilson, R., Chen, Y.-F., Wang, L.-F., Yu, Z.-L., …Lun, Z.-R. (2017). Nitric oxide blocks the development of the human parasite Schistosoma japonicum. Proceedings of the National Academy of Sciences of the United States of America, 114(38), 10214-10219. https://doi.org/10.1073/pnas.1708578114

• Journal Article Type: Article
• Acceptance Date: Aug 4, 2017
• Online Publication Date: Sep 5, 2017
• Publication Date: Sep 19, 2017
• Deposit Date: Sep 15, 2017
• Publicly Available Date: Sep 15, 2017
• Journal: Proceedings of the National Academy of Sciences
• Print ISSN: 0027-8424
• Publisher: National Academy of Sciences
• Volume: 114
• Issue: 38
• Pages: 10214-10219
• DOI: https://doi.org/10.1073/pnas.1708578114
• Publisher URL: http://dx.doi.org/10.1073/pnas.1708578114
• Related Public URLs: http://www.salford.ac.uk/environment-life-sciences/els-academics/geoff-hide; http://www.pnas.org/
• Additional Information: Funders : National Key R&D Program of China;National Science Foundation of China; Projects : Nitric oxide blocks the development of the human parasite Schistosoma japonicum; Grant Number: 2016YFC1200500; Grant Number: 31472058, 31402029, 31672276, and 81572014