Related Articles Loss to Self-Heal Malaria upon Taurine Transporter Deletion.

Infect Immun. 2010 Jan 25;

Authors: Delic D, Warskulat U, Borsch E, Al-Qahtani S, Al-Quraishy S, Häussinger D, Wunderlich F

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 lowering of the circulating taurine from 540 to 264 mumol/l and infections cause a additional lowering to 192 mumol/l. Peak parasitemia in taut(-/-) mice is approximately 60% higher than in taut(+/+) mice, which is associated with increased systemic levels of TNFalpha and IL-1beta as well as liver injuries. The latter manifest themselves as increased systemic levels of ammonia, perturbed capacity to entrap injected particles, increased expression of genes encoding TNFalpha, IL-1beta, IL-6, iNOS, NFkappaB, and VDR. Autopsy reveals multi-organ failure as cause of death of malaria-infected taut(-/-) mice. Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency, however, due to taut deletion impairs eryptosis of P. chabaudi parasitized erythrocytes and expedites increases in systemic levels of TNFalpha, IL-1beta, and ammonia presumably contributing to multi-organ failure in P. chabaudi-infected taut(-/-) mice.

PMID: 20100858 [PubMed - as supplied by publisher]