Understanding the factors that regulate the induction, quality, and longevity of antiviral T cell responses is essential for devising rational strategies to prevent or combat infections. In this study, we show that interleukin-21 (IL-21), likely produced by CD4+ T cells, directly influences the generation of polyfunctional CD8+ T cells and that the number of CD4+ T cells that produce IL-21 differs markedly between acute and chronic infections. IL-21 regulates the development of CD8+ T cell exhaustion and the ability to contain chronic lymphocytic choriomeningitis virus infection. Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control.

Chronic viral infections provoke a war of attrition between cytotoxic T cells (the CD8+ subclass) of the immune system and infected host cells. Although the CD8+ T cell response gradually whittles away at the viral load, the cells progressively become "exhausted" and lose function during a chronic infection (1). This exhaustion becomes more severe in the absence of helper CD4+ T cells, potentially leading to viral persistence and loss of virus-specific CD8+ T cells (1, 2). But how do CD4+ cells help? Three reports in this issue, by Elsaesser et al. on page 1569 (3), Yi et al. on page 1572 (4), and Fröhlich et al. on page 1576 (5), suggest an unexpected role for a specific cytokine produced by CD4+ T cells called interleukin-21 (IL-21) in controlling chronic viral infections.

Ebola Zaire virus causes severe hemorrhagic fever in humans that is fatal in almost 90% of cases. The rapid spread of the virus to macrophages and dendritic cells results in the release of high levels of inflammatory cytokines, causing shock and bleeding. The ability of Ebola virus to overwhelm host defenses is believed to result from its suppression of the type I interferon (IFN) response. The Ebola viral protein VP35 is known to block IFN responses, but the precise mechanisms have not been identified. We expressed VP35 in mouse dendritic cells and found that the cells failed to develop a normal IFN response when infected with Newcastle Disease virus. By a yeast two-hybrid system and other biochemical experiments, we showed that the blockade resulted from the conjugation of a Small Ubiquitin-like Modifier (SUMO) protein to IRF-7, the principal cellular factor required for IFN gene expression. However, the cells were still able to activate NF-κB, a transcription factor responsible for the release of proinflammatory cytokines. Our findings provide a first example where a virus hijacks the host SUMO system to undermine innate immunity, and help to explain how Ebola virus spreads rapidly in lymphoid tissues to cause a lethal inflammatory syndrome.

Antioxidants are considered as health benefactor from time immemorial. To protect yourself from diseases and stay healthy and fit, make it a point to include antioxidant supplements in your everyday diet. Keep a good physical and mental well being by consuming antioxidant foods.

A new technique creates all-purpose antibodies that can be activated at a moment’s notice.

Systemic acquired resistance (SAR) is a broad-spectrum plant immune response involving profound transcriptional changes that are regulated by the coactivator NPR1. Nuclear translocation of NPR1 is a critical regulatory step, but how the protein is regulated in the nucleus is unknown. Here, we show that turnover of nuclear NPR1 protein plays an important role in modulating transcription of its target genes. In the absence of pathogen challenge, NPR1 is continuously cleared from the nucleus by the proteasome, which restricts its coactivator activity to prevent untimely activation of SAR. Surprisingly, inducers of SAR promote NPR1 phosphorylation at residues Ser11/Ser15, and then facilitate its recruitment to a Cullin3-based ubiquitin ligase. Turnover of phosphorylated NPR1 is required for full induction of target genes and establishment of SAR. These invivo data demonstrate dual roles for coactivator turnover in both preventing and stimulating gene transcription to regulate plant immunity.

The eel-like sea lamprey may not have as primitive an immune system as many scientists thought. In this week's issue of Nature, researchers report that the lamprey has two distinct classes of immune cells, with similar properties to the T and B cells at the heart of the so-called adaptive immune response in people. T and B cells are found only in jawed vertebrates such as humans, where they protect against harmful bacteria and other invaders. Yet, the lamprey is a jawless vertebrate and seems to have evolved its own defense strategies. Immunologists say the find could shed light on how the human immune system evolved in the first place.

Many human genes have adapted to the constant threat of exposure to infectious agents; according to the "hygiene hypothesis," lack of exposure to parasites in modern settings results in immune imbalances, augmenting susceptibility to the development of autoimmune and allergic conditions. Here, by estimating the number of pathogen species/genera in a specific geographic location (pathogen richness) for 52 human populations and analyzing 91 interleukin (IL)/IL receptor genes (IL genes), we show that helminths have been a major selective force on a subset of these genes. A population genetics analysis revealed that five IL genes, including IL7R and IL18RAP, have been a target of balancing selection, a selection process that maintains genetic variability within a population. Previous identification of polymorphisms in some of these loci, and their association with autoimmune conditions, prompted us to investigate the relationship between adaptation and disease. By searching for variants in IL genes identified in genome-wide association studies, we verified that six risk alleles for inflammatory bowel (IBD) or celiac disease are significantly correlated with micropathogen richness. These data support the hygiene hypothesis for IBD and provide a large set of putative targets for susceptibility to helminth infections.

Thank parasites for making our interleukins into the inflammatory defenders they are today, according to a population genetics study by Fumagalli et al. However, you might also blame the bugs for sculpting some of those genes into risk factors for intestinal disorders. Parasite-driven selection leaves a footprint on host genomes in the form of single-nucleotide polymorphisms (SNPs). Genetic variation (multiple SNPs) at a particular locus can be maintained within a population if a certain SNP helps the host fend off infections in one environment, but hinders the host in another environment with different parasitic pressures. Here, Fumagalli et al. sift through 1,052 SNPs in human interleukin genes from roughly 1,000 people worldwide. Of 91 genes assessed, 44 bore signatures of selection, meaning that the genetic variation was due neither to chance nor to the migration of populations over time. And some of that variation correlated with parasitic diversity, indicating that parasites drove selection. Parasitic worms appear to have applied a more powerful selective pressure on certain interleukin genes than did viruses, bacteria, or fungi (assuming that pathogen diversity has remained relatively stable over time). That isn’t surprising, says senior author Manuela Sironi, because worms typically evolve slower than bacteria or viruses, giving their hosts time to adapt. Worm-driven selection of SNPs in genes encoding IL-10 and IL-4 might have been predicted based on their known roles in promoting the Th2 responses needed to fight off worm infections. Without the IL-4 receptor, for example, mice cannot expel certain nematodes. SNPs in the gene encoding IL-19 correlated strongly with worm diversity as well. Because this cytokine promotes inflammation in the skin, the authors suggest that it might protect against skin-borne infections. Surprisingly, six of the nine known risk alleles for Crohn’s and celiac disease also appeared to be selected for by pathogen diversity. Like most of these disease-associated SNPs, those in the Crohn’s risk gene IL12B correlated more closely with viral, bacterial, and fungal diversity than with worm diversity. In theory, these risky alleles have been maintained because they promote vigorous Th1 responses, which help fend off viruses and bacteria. But overly exuberant Th1 responses also contribute to inflammatory bowel diseases. Other pathogen-selected SNPs were more puzzling. For example, SNPs in the gene encoding an IL receptor-associate protein, IL1RAPL1, correlated with worm diversity, yet the protein functions in brain development and has no reported role in the immune response.