Abstract
Toxoplasma gondii infects humans and warm blooded animals causing devastating disease worldwide. It has long been a mystery as to why the peritoneal macrophages of rats are naturally resistant to T. gondii infection while those of mice are not. Here, we report that high expression levels and activity of inducible nitric oxide synthase (iNOS) and low levels of arginase-1 (Arg 1) activity in the peritoneal macrophages of rats are responsible for their resistance against T. gondii infection, due to high nitric oxide and low polyamines within these cells. The opposite situation was observed in the peritoneal macrophages of mice. This discovery of the opposing functions of iNOS and Arg 1 in rodent peritoneal macrophages may lead to a better understanding of the resistance mechanisms of mammals, particularly humans and livestock, against T. gondii and other intracellular pathogens.
Highlights
Persistent infection is one hallmark of the Apicomplexan protozoan Toxoplasma gondii, and it is required for maintaining the parasite’s life cycle
Since there is competition for the substrate between inducible nitric oxide synthase (iNOS) and arginase, we analyzed the level of iNOS expression and nitric oxide (NO) production in non-activated peritoneal macrophages isolated from 5 strains of rat (Sprague-Dawley (SD), Lewis, Wistar, Fischer 344 (F344) and Brown Norway (BN)) and 4 strains of mouse (Swiss, BALB/c, C57BL/6 and NIH)
Previous research has shown that rat peritoneal macrophages do not support the multiplication of Toxoplasma gondii in vitro, but those of mice do [6,7]
Summary
Persistent infection is one hallmark of the Apicomplexan protozoan Toxoplasma gondii, and it is required for maintaining the parasite’s life cycle. This feature and the ability to infect a broad spectrum of warm-blooded vertebrates, including up to 30% of the world’s human population, as well as to develop within any nucleated cell type investigated so far, shows T. gondii to be one of the most successful obligate intracellular parasites [1]. T. gondii is a major opportunistic pathogen of fetuses from recently infected mothers, and of immunocompromised patients, i.e. those with organ transplantation and AIDS [2,3] In these individuals, the immune system is unable to control the parasite efficiently, leading to unrestricted parasite multiplication and to life-threatening disease. The mechanism of rat macrophage resistance to T. gondii remains yet to be determined
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