Nitric oxide blocks the development of the human parasite Schistosoma japonicum

Significance Viable egg production by Schistosoma species is the key pathogenic process causing granuloma formation in permissive hosts (e.g., mice), while nonpermissive hosts [e.g., Norway rats ( Rattus norvegicus )] avoid such sequelae. Using inducible nitric oxide synthase knockout (iNOS −/− ) rats, we demonstrate that high expression levels of iNOS in rats play an important role in blocking the egg-induced granuloma formation of Schistosoma japonicum . The nitric oxide, produced by iNOS, inhibits parasite growth, reproductive organ development, egg production, and viability by interfering with mitochondrial function. This study solves the puzzle as to why rats are naturally resistant to S. japonicum infection and provides insights for understanding the pathogenesis of human schistosomiasis and the interactions between host and parasite.