Novel Gene Expressed in Spleen Cells Mediating Acquired Testosterone-Resistant Immunity toPlasmodium chabaudiMalaria

Krücken, Jürgen; Schmitt-Wrede, Hans-Peter; Markmann-Mulisch, Ulrich; Wunderlich, Frank

doi:10.1006/bbrc.1996.5876

Cited by 33 publications

(45 citation statements)

References 18 publications

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“…Three members of this gene family have been described: Ian1 is a thymic selection marker expressed at various stages of thymocyte development (28). Ian2 is induced in B-lymphocytes by infections of Plasmodium chabaudi malaria (29,30). Ian3 (28) has not been functionally characterized.…”

Section: Resultsmentioning

confidence: 99%

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Hornum¹,

Rømer

Markholst³

2002

Diabetes

152

143

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1Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling human type 1 diabetes. They also exhibit lifelong T-cell lymphopenia. Functional and genetic data support the hypothesis that the gene responsible for the lymphopenia, Lyp, is also a diabetes susceptibility gene, named Iddm1. We constructed a 550-kb P1-derived artificial chromosome contig of the region. Here, we present a corrected genetic map reducing the genetic interval to 0.2 cM and the physical interval to 150 -290 kb. A total of 13 genes and six GenomeScan models are assigned to the homologous human DNA segment on HSA7q36.1, 8 of which belong to the family of immune-associated nucleotides (Ian genes). Two of these are orthologous to mouse Ian1 and -4, both excellent candidates for Iddm1. In normal rats, they are expressed in the thymus and T-cell regions of the spleen. In the thymus of lymphopenic rats, Ian1 exhibits wild-type expression patterns, whereas Ian4 expression is reduced. Mutational screening of their coding sequences revealed a frameshift mutation in Ian4 among lymphopenic rats. The mutation results in a truncated protein in which the COOH-terminal 215 amino acids-including the anchor localizing the protein to the outer mitochondrial membrane-are replaced by 19 other amino acids. We propose that Ian4 is identical to Iddm1.

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Section: Resultsmentioning

confidence: 99%

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Hornum¹,

Rømer

Markholst³

2002

Diabetes

152

143

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“…RNA (10 g) was denatured with glyoxal and separated as described previously (24). Hybridization was carried out overnight at 65°C using ExpressHyb solution (Clontech) and [␣-…”

Section: Methodsmentioning

confidence: 99%

Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria

et al. 2005

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Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-m-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an ϳ3-to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosteronemediated suppression of resistance against blood-stage malaria.

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“…Furthermore, testosterone-induced susceptibility appears to be due to hormonal imprinting, as testosterone treatment of female mice for 3 weeks followed by 9 weeks without treatment, during which time testosterone falls to pretreatment levels, continues to make female mice susceptibile to challenge with P. chabaudi (19). Recently, a novel putative transmembrane protein (IAP30) which is induced on murine spleen cells during P. chabaudi infection in the presence of testosterone has been identified (75,76). The importance of gender-influenced susceptibility to P. chabaudi is emphasized in experiments that demonstrate that the efficacy of vaccination against this parasite is as high as 90% in female mice but only 55% in males.…”

Section: Plasmodiummentioning

confidence: 99%

Sex-Associated Hormones and Immunity to Protozoan Parasites

2001

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Numerous epidemiological and clinical studies have noted differences in the incidence and severity of parasitic diseases between males and females. Although in some instances this may be due to gender-associated differences in behavior, there is overwhelming evidence that sex-associated hormones can also modulate immune responses and consequently directly influence the outcome of parasitic infection. Animal models of disease can often recreate the gender-dependent differences observed in humans, and the role of sex-associated hormones can be confirmed by experimentally altering their levels. Under normal circumstances, levels of sex hormones not only differ between males and females but vary according to age. Furthermore, not only are females of reproductive age subject to the regular hormonal cycles which control ovulation, they are also exposed to dramatically altered levels during pregnancy. It is thus not surprising that the severity of many diseases, including those caused by parasites, has been shown to be affected by one or more of these circumstances. In addition, infection with many pathogens has been shown to have an adverse influence on pregnancy. In this article we review the impact of sex-associated hormones on the immune system and the development and maintenance of immunity to the intracellular protozoan parasites Toxoplasma gondii, Plasmodium spp., and Leishmania spp

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Novel Gene Expressed in Spleen Cells Mediating Acquired Testosterone-Resistant Immunity toPlasmodium chabaudiMalaria

Cited by 33 publications

References 18 publications

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria

Sex-Associated Hormones and Immunity to Protozoan Parasites

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