Nitric oxide blocks the development of the human parasiteSchistosoma japonicum

Author:

Shen Jia,Lai De-HuaORCID,Wilson R. Alan,Chen Yun-Fu,Wang Li-Fu,Yu Zi-Long,Li Mei-Yu,He Ping,Hide Geoff,Sun Xi,Yang Ting-Bao,Wu Zhong-Dao,Ayala Francisco J.,Lun Zhao-Rong

Abstract

Human schistosomiasis, caused bySchistosomaspecies, 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 toSchistosoma japonicuminfection, 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 inS. 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 inS. japonicumbut also offers insights into a better understanding of host–parasite interactions and drug development strategies against schistosomiasis.

Funder

National Research and Development Plan of China

National Science Foundation of China

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference58 articles.

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