Description:
<jats:title>ABSTRACT</jats:title><jats:p>Deletion of the taurine transporter gene (<jats:italic>taut</jats:italic>) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show that<jats:italic>taut</jats:italic><jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup>mice have lost their ability to self-heal blood-stage infections with<jats:italic>Plasmodium chabaudi</jats:italic>malaria. All<jats:italic>taut</jats:italic><jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup>mice succumb to infections during crisis, while about 90% of the control<jats:italic>taut<jats:sup>+/+</jats:sup></jats:italic>mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion of<jats:italic>taut</jats:italic>, however, results in the lowering of circulating taurine levels from 540 to 264 μmol/liter, and infections cause additional lowering to 192 μmol/liter. Peak parasitemia levels in<jats:italic>taut</jats:italic><jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup>mice are approximately 60% higher than those in<jats:italic>taut<jats:sup>+/+</jats:sup></jats:italic>mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels, as well as with liver injuries. The latter manifest as increased systemic ammonia levels, a perturbed capacity to entrap injected particles, and increased expression of genes encoding TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), NF-κB, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infected<jats:italic>taut</jats:italic><jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup>mice. Our data indicate that<jats:italic>taut</jats:italic>-controlled taurine homeostasis is essential for resistance to<jats:italic>P. chabaudi</jats:italic>malaria. Taurine deficiency due to<jats:italic>taut</jats:italic>deletion, however, impairs the eryptosis of<jats:italic>P. chabaudi</jats:italic>-parasitized erythrocytes and expedites increases in systemic TNF-α, IL-1β, and ammonia levels, presumably contributing to multiorgan failure in<jats:italic>P. chabaudi</jats:italic>-infected<jats:italic>taut</jats:italic><jats:sup>−</jats:sup><jats:sup>/</jats:sup><jats:sup>−</jats:sup>mice.</jats:p>