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Parasites exploit biochemical loophole to trick immune system

A team of German and American researchers has discovered a key mechanism by which some pathogens trick the immune system and block proper functioning of immune cells. In the advance online publication of the journal Nature Immunology, they explain that the intracellular microo...

A team of German and American researchers has discovered a key mechanism by which some pathogens trick the immune system and block proper functioning of immune cells. In the advance online publication of the journal Nature Immunology, they explain that the intracellular microorganisms disrupt the biochemical workings of one of the body's most important defence mechanisms, the macrophages (or so-called 'eater cells'), by activating an endogenous enzyme. The discovery could pave the way to more effective treatments of tuberculosis and toxoplasmosis. Macrophages attack and consume bacteria and parasites with the help of enzymes and nitric oxide. However, Mycobacterium tuberculosis, the main cause of tuberculosis, and Toxoplasma gondii, a unicellular parasite that can cause toxoplasmosis, live within macrophages themselves. Studying the effect of these pathogens on macrophages in the culture dish and in mice, the scientists found that the microorganisms activate an enzyme called arginase in the eater cells. Arginase occurs naturally in macrophages and is used to regulate the production of nitric oxide. Under normal conditions, arginase is activated when the macrophages produce too much nitric oxide and suppresses its production. It is this mechanism that benefits the microorganisms. 'Although the findings are basic, they suggest that it might be feasible to develop drugs to block such pathogens' biochemical subversion, restoring nitric oxide production and empowering macrophages to attack the invaders,' said Dr Peter Murray of St. Jude Children's Research Hospital in Memphis, US. He added that no one had previously explored the possibility that intracellular pathogens could directly exploit arginase activation as a defence. 'Our findings reveal that these pathogens have evolved to exploit a biological loophole in the immune system,' explains Dr Murray. 'This discovery offers two important insights. It reaffirms the notion that pathogens have an incredibly diverse way of manipulating their hosts, and it reveals a new pathway by which a pathogen can induce an enzyme that is normally not present in those macrophages and use the induction of that enzyme to its advantage.' The scientists hope that their discovery will help to develop targeted drugs to specifically inhibit the ability of pathogens to induce arginase in macrophages. Combining such drugs with existing treatments for these diseases might be a significant step forward. In the laboratory, their strategy has already been successful. Genetically engineered mice that lack arginase in their macrophages were more resistant to both tuberculosis and toxoplasmosis than their non-modified counterparts.

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