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Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10214-10219. doi: 10.1073/pnas.1708578114. Epub 2017 Sep 5.

Nitric oxide blocks the development of the human parasite Schistosoma japonicum.

Author information

1
Center for Parasitic Organisms, State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China.
2
Department of Parasitology, Key Laboratory of Tropical Disease Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People's Republic of China.
3
Centre for Immunology and Infection, Department of Biology, University of York, Heslington, York YO10 5DD, United Kingdom.
4
Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, United Kingdom.
5
Department of Parasitology, Key Laboratory of Tropical Disease Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People's Republic of China; fjayala@uci.edu wuzhd@mail.sysu.edu.cn lsslzr@mail.sysu.edu.cn.
6
Department of Ecology and Evolutionary Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697 fjayala@uci.edu wuzhd@mail.sysu.edu.cn lsslzr@mail.sysu.edu.cn.
7
Center for Parasitic Organisms, State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China; fjayala@uci.edu wuzhd@mail.sysu.edu.cn lsslzr@mail.sysu.edu.cn.

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.

KEYWORDS:

Schistosoma japonicum; granuloma formation; mitochondria; rat; schistosomiasis

PMID:
28874579
PMCID:
PMC5617295
DOI:
10.1073/pnas.1708578114
[Indexed for MEDLINE]
Free PMC Article

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