Loss of Ability To Self-Heal Malaria upon Taurine Transporter Deletion

• Published in: Infection and Immunity Vol. 78; no. 4; pp. 1642 - 1649
• Main Authors: Delić, Denis, Warskulat, Ulrich, Borsch, Elena, Al-Qahtani, Saad, Al-Quraishi, Saleh, Häussinger, Dieter, Wunderlich, Frank
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.04.2010; American Society for Microbiology (ASM)
• Subjects: Ammonia - blood; Animals; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Host Response and Inflammation; Human protozoal diseases; Infectious diseases; Interleukin-1beta - blood; Liver - pathology; Malaria; Malaria - immunology; Malaria - mortality; Malaria - pathology; Medical sciences; Membrane Glycoproteins - deficiency; Membrane Transport Proteins - deficiency; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Multiple Organ Failure; Parasitemia; Parasitic diseases; Plasmodium chabaudi - immunology; Plasmodium chabaudi - pathogenicity; Protozoal diseases; Sequence Deletion; Survival Analysis; Taurine - blood; Tumor Necrosis Factor-alpha - blood; Infection; Taurine; Protozoal disease; Malaria; Aminoacid; Deletion; Parasitosis; Mutation; Immunity; Carrier protein
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01159-09

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.