| First Author | Delic D | Year | 2010 |
| Journal | Infect Immun | Volume | 78 |
| Issue | 4 | Pages | 1642-9 |
| PubMed ID | 20100858 | Mgi Jnum | J:193590 |
| Mgi Id | MGI:5468795 | Doi | 10.1128/IAI.01159-09 |
| Citation | Delic D, et al. (2010) Loss of ability to self-heal malaria upon taurine transporter deletion. Infect Immun 78(4):1642-9 |
| abstractText | Deletion of the taurine transporter gene (taut) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show that taut-/- mice have lost their ability to self-heal blood-stage infections with Plasmodium chabaudi malaria. All taut-/- mice succumb to infections during crisis, while about 90% of the control taut(+/+) mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion of taut, however, results in the lowering of circulating taurine levels from 540 to 264 micromol/liter, and infections cause additional lowering to 192 micromol/liter. Peak parasitemia levels in taut-/- mice are approximately 60% higher than those in taut(+/+) mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) 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-alpha, IL-1beta, IL-6, inducible nitric oxide synthase (iNOS), NF-kappaB, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infected taut-/- mice. Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency due to taut deletion, however, impairs the eryptosis of P. chabaudi-parasitized erythrocytes and expedites increases in systemic TNF-alpha, IL-1beta, and ammonia levels, presumably contributing to multiorgan failure in P. chabaudi-infected taut-/- mice. |
