In:
Infection and Immunity, American Society for Microbiology, Vol. 78, No. 4 ( 2010-04), p. 1642-1649
Abstract:
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 μmol/liter, and infections cause additional lowering to 192 μmol/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-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 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-α, IL-1β, and ammonia levels, presumably contributing to multiorgan failure in P. chabaudi -infected taut − / − mice.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.01159-09
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2010
detail.hit.zdb_id:
1483247-1
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