title: Loss of ability to self-heal malaria upon taurine transporter deletion.
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 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.
authors.affiliation: Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr 5, 40225 Düsseldorf, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Delic
authors.forename: Ulrich
authors.initials: U
authors.lastname: Warskulat
authors.forename: Elena
authors.initials: E
authors.lastname: Borsch
authors.forename: Saad
authors.initials: S
authors.lastname: Al-Qahtani
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Quraishi
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Frank
authors.initials: F
authors.lastname: Wunderlich
mesh_terms: D000641:Ammonia / Q000097:blood; D000818:Animals; D005260:Female; D053583:Interleukin-1beta / Q000097:blood; D008099:Liver / Q000473:pathology; D008288:Malaria / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency*; D026901:Membrane Transport Proteins / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009102:Multiple Organ Failure; D018512:Parasitemia; D016788:Plasmodium chabaudi / Q000276:immunology* / Q000472:pathogenicity*; D017384:Sequence Deletion; D016019:Survival Analysis; D013654:Taurine / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099247:Taurine Transporters
chemical_list: D000641:Ammonia; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D014409:Tumor Necrosis Factor-alpha; D000099247:Taurine Transporters