Evading plant defence: Infestation of poisonous milkweed fruits (Asclepiadaceae) by the fruit fly Dacus siliqualactis (Diptera: Tephritidae).

To cope with toxic metabolites plants use for defence, herbivorous insects employ various adaptive strategies. For oviposition, the fruit fly Dacus siliqualactis (Tephritidae) uses milkweed plants of the genus Gomphocarpus (Asclepiadaceae) by circumventing the plant's physical (gluey latex) and chemical (toxic cadenolides) defence. With its long, telescope-like ovipositor, the fly penetrates the exo- and endocarp of the fruit and places the eggs on the unripe seeds located in the centre of the fruit. Whereas most plant parts contain high concentrations of cardenolides such as gomphoside, calotropin/calacatin and gomphogenin, only the seeds exhibit low cardenolide levels. By surmounting physical barriers (fruit membranes, latex), the fly secures a safe environment and a latex-free food source of low toxicity for the developing larvae. One amino acid substitution (Q111V) at the cardenolide binding site of the fly's Na+, K+-ATPase was detected, but the significance of that substitution: reducing cardenolide sensitivity or not, is unclear. However, poisoning of the larvae by low levels of cardenolides is assumed to be prevented by non-resorption and excretion of the polar cardenolides, which cannot passively permeate the midgut membrane. This example of an insect-plant interaction demonstrates that by morphological and behavioural adaptation, a fruit fly manages to overcome even highly effective defence mechanisms of its host plant.

A genetic basis for IFN-gamma production and T-bet expression in humans.

Th1 and Th2 cytokines secreted by polarized effector T cells play a pivotal role in the development of autoimmune and allergic diseases. However, the genetic basis of cytokine production by T lymphocytes in humans is poorly understood. In this study, we investigated the genetic contribution to cytokine production and regulation of T cell-specific transcription factors in a prospective twin study. We found a substantial genetic contribution to the production of Th1 cytokines such as IFN-gamma and TNF-alpha with heritabilities of 0.85 (95% confidence intervals, 0.74-0.95) and 0.72 (0.50-0.93), respectively, whereas no genetic influence on production of the Th2 signature cytokine IL-4 was observed. Furthermore, the intrapair variability in IFN-gamma production by isolated T cells was lower in monozygotic than in dizygotic twins. In contrast to GATA-3, NFAT, and NF-kappaB, intrapair variability of T-bet, the master transcription factor of Th1 cells, was very low among monozygotic and high among dizygotic twins, indicative of a strong genetic influence on T-bet (heritability 0.93, 95% confidence interval, 0.84-1.0). Our data provide novel insights into the genetic regulation of human Th cell polarization. These data suggest that signature cytokines and cytokine signaling events of Th1 rather than Th2 cells are genetically determined and implicate that Th2-associated diseases in humans might be due to genetic variations in Th1 cytokine regulation via T-bet. This concept is highlighted by the recent finding that inactivation of the T-bet gene in mice results in development of clinical hallmark features of asthma.

A functional polymorphism in the IL-10 promoter influences the response after vaccination with HBsAg and hepatitis A.

The immune response to hepatitis B surface antigen (HBsAg) is mostly genetically determined. Interleukin 10 (IL-10) is a central immunoregulatory cytokine with important effects on B-cells. We have studied the influence of IL-10 promoter polymorphisms on the immune response to HBsAg and hepatitis A vaccination. We vaccinated 202 twin pairs in an open prospective study with a combined recombinant HBsAg/inactivated hepatitis A vaccine. IL-10 promoter polymorphisms were investigated in all individuals and their influence on anti-HBs, and anti-HAV responsiveness was studied. In the multiple regression analysis accounting for smoking, gender, body mass index and age, the ACC haplotype (-1082, -819 and -592) had a strong influence on anti-HBs production. Individuals carrying the ACC haplotype had anti-HBs titres almost twice as high as individuals without this haplotype. In contrast, anti-HAV production was suppressed by the presence of the -1082A allele in comparison with individuals homozygous for the -1082G allele. The contribution of the shared IL-10 promoter haplotype accounted for 27% of the genetic influence on anti-HBs antibody response. In conclusion, genetic variability in the IL-10 promoter is an important modulator of the immune response against hepatitis viral antigens.

Studies on the cardenolide sequestration in African milkweed butterflies (Danaidae).

Butterflies of the Danaidae family are considered to be toxic or distasteful due to the presence of cardiac glycosides sequestered from their larval food plants. Alcoholic extracts of specimens of Danaus chrysippus aegyptius and Amauris ochlea ochlea from southern Africa (Namibia, S.-Africa, Mozambique) were analyzed by thin-layer chromatography for these cardenolides. But only 4 of 75 specimens of D. chrysippus aegyptius contained trace amounts, all others including 13 specimens of A. ochlea ochlea were negative. Genetic analysis of the ouabain binding site of the Na(+), K(+)-ATPase revealed that both species do not present an amino acid replacement at the position 122, which otherwise makes the enzyme insensitive to cardenolides suggesting that other strategies of toxin tolerance must have been developed.

Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins.

BACKGROUND: The course of viral hepatitis is thought to be affected by genetic host variability and, in particular, by genes of the major histocompatibility locus. Hepatitis A and B vaccination is a useful model to study the effect of host factors on the immune response to viral antigens. We aimed to assess the heritability of the HBsAg (anti-HBs) and anti-hepatitis A virus (anti-HAV) immune response and to estimate the effect of the HLA-DRB1 locus and other genetic loci unlinked to HLA. METHODS: We did an open prospective study and vaccinated 202 twin pairs with a combined recombinant HBsAg/inactivated hepatitis A vaccine. We measured antibodies to HBsAg and HAV and determined HLA-DRB1* alleles. Heritability was calculated based on variance of antibody response within pairs. Model-fitting analyses were done to analyse genetic and environmental components of vaccine responses. FINDINGS: Anti-HBs and anti-HAV showed heritabilities of 0.61 (95% CI 0.41 to 0.81) and 0.36 (-0.02 to 0.73), respectively. For the anti-HBs immune response, 60% of the phenotypic variance was explained by additive genetic and 40% by non-shared environmental effects. The heritability of the HBsAg vaccine response accounted for by the DRB1* locus was estimated to be 0.25, leaving the remaining heritability of 0.36 to other gene loci. INTERPRETATION: Genetic factors have a strong effect on the immune response to HBsAg. Although genes encoded within the MHC are important for this immune response, more than half the heritability is determined outside this complex. Identification of these genes will help us to understand regulation of immune responses to viral proteins.