Hot off the presses! May 01 Nat Rev Immunol

The May 01 issue of the Nat Rev Immunol is now up on Pubget (About Nat Rev Immunol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Immunol 11(5):297 (2011)
  
• Granulocytes: A weighty role for eosinophils | PDF (115 KB)
  - Nat Rev Immunol 11(5):299 (2011)
  New evidence published in Science showing that eosinophils can migrate to adipose tissue to maintain glucose homeostasis adds to our increasing appreciation of the links between immune and metabolic systems. We know that adipose tissue macrophages are an important component of the chronic low grade inflammation that characterizes the metabolic syndrome; this study now shows that eosinophils can modulate the phenotype of macrophages in adipose tissue to restrict this inflammation.
• Cell death and immunity: Caspase 8 and RIPK3 play with life and death | PDF (156 KB)
  - Nat Rev Immunol 11(5):300 (2011)
  Programmed cell death can be mediated by different mechanisms, including apoptosis, autophagy and programmed necrosis (also termed necroptosis). Although caspase 8 initiates T cell apoptosis following death receptor ligation, caspase 8-deficient T cells display decreased survival after stimulation compared with wild-type T cells.
• T cell signalling: Heavy metal rocks T cells | PDF (151 KB)
  - Nat Rev Immunol 11(5):300 (2011)
  During the flu season, supermarket shelves are heavily laden with food supplements proclaiming the wonders of zinc for immune health, but the precise mechanisms by which zinc enhances immune function are poorly understood. Yu et al.
• Immunotherapy for metastatic melanoma approved | PDF (82 KB)
  - Nat Rev Immunol 11(5):300 (2011)
  Patients with melanoma have been given hope with the news that ipilimumab (Yervoy; Bristol-Myers Squibb), a monoclonal antibody specific for cytotoxic T lymphocyte antigen 4 (CTLA4), has been approved by the US Food and Drug Administration (FDA) (FDA website, 25 Mar 2011).
• T cell responses | Vaccines | PDF (95 KB)
  - Nat Rev Immunol 11(5):301 (2011)
  Autocrine transforming growth factor-β1 promotes in vivo Th17 cell differentiation Gutcher, I.et al. Immunity 34, 396–408 (2011)
• Antigen presentation: Cross-dress to impress | PDF (225 KB)
  - Nat Rev Immunol 11(5):302 (2011)
  The presentation of MHC class I-bound antigen to CD8+ T cells by professional antigen-presenting cells (APCs) can occur through two mechanisms: direct presentation of antigen by infected APCs; and cross-presentation of antigen that is acquired by phagocytosis of infected cells and then processed and presented by MHC class I molecules. A third mechanism termed 'cross-dressing' has been proposed, which involves the transfer of preformed peptide–MHC class I complexes from the surface of infected cells to uninfected APCs without the need for further antigen processing.
• Allergy: Shocking behaviour | PDF (337 KB)
  - Nat Rev Immunol 11(5):302 (2011)
  Anaphylaxis is a life-threatening systemic allergic reaction that is classically associated with IgE-mediated activation of mast cells and histamine release. In addition, IgG1 antibodies can induce anaphylaxis, and it has been reported that this depends on the activation of basophils.
• Tumour immunology: Bad company | PDF (198 KB)
  - Nat Rev Immunol 11(5):303 (2011)
  The presence or absence of different types of immune cells is known to influence the outcome for patients with cancer, but we are still some way from understanding the complex interactions between immune cell subsets and how these cells affect tumour growth and regression. A paper published in Cancer Discovery shows that the response of patients with breast cancer to specific chemotherapies is influenced by the subsets of leukocytes that are present in the tumour.
• Innate immunity: Intracellular MHC class II: not just hiding | PDF (339 KB)
  - Nat Rev Immunol 11(5):304 (2011)
  Cell surface expression of MHC class II molecules on antigen-presenting cells (APCs) is essential for the induction of adaptive immune responses. Surface MHC class II molecules present antigenic peptides to CD4+ T cells and, following ligation, mediate reverse signal transduction that regulates cell adhesion, cytokine production and co-stimulation.
• Antiviral immunity: Flora against the flu | PDF (253 KB)
  - Nat Rev Immunol 11(5):304 (2011)
  The intestinal flora has been shown to shape the immune responses in the gut, mainly by providing activation signals for innate pattern recognition receptors. A study published in PNAS now suggests that the immunological role of commensal bacteria is not restricted to the intestinal mucosa, by showing that these bacteria can influence the adaptive immune responses to influenza virus in the lung.
• Allergy: Crystal clear culprit | PDF (317 KB)
  - Nat Rev Immunol 11(5):304 (2011)
  The deposition of crystals of uric acid (a by-product of metabolism that is expelled by stressed cells) is known to trigger the neutrophilic inflammation associated with gout. Now, Lambrecht, Hammad and co-workers have shown that uric acid crystals can also promote T helper 2 (TH2)-type immune responses and allergic airway disease in mice.
• Dendritic cells | Cell migration | Immunotherapy | PDF (86 KB)
  - Nat Rev Immunol 11(5):305 (2011)
  Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity Flach, T. L.et al. Nature Med. 17, 479–487 (2011)
• Design principles of adaptive immune systems
  - Nat Rev Immunol 11(5):307 (2011)
  Both jawless vertebrates, such as lampreys and hagfish, and jawed vertebrates (encompassing species as diverse as sharks and humans) have an adaptive immune system that is based on somatically diversified and clonally expressed antigen receptors. Although the molecular nature of the antigen receptors and the mechanisms of their assembly are different, recent findings suggest that the general design principles underlying the two adaptive immune systems are surprisingly similar. The identification of such commonalities promises to further our understanding of the mammalian immune system and to inspire the development of new strategies for medical interventions targeting the consequences of faulty immune functions.
• Illuminating viral infections in the nervous system
  - Nat Rev Immunol 11(5):318 (2011)
  Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses.
• Harnessing the biology of IL-7 for therapeutic application
  - Nat Rev Immunol 11(5):330 (2011)
  Interleukin-7 (IL-7) is required for T cell development and for maintaining and restoring homeostasis of mature T cells. IL-7 is a limiting resource under normal conditions, but it accumulates during lymphopaenia, leading to increased T cell proliferation. The administration of recombinant human IL-7 to normal or lymphopenic mice, non-human primates and humans results in widespread T cell proliferation, increased T cell numbers, modulation of peripheral T cell subsets and increased T cell receptor repertoire diversity. These effects raise the prospect that IL-7 could mediate therapeutic benefits in several clinical settings. This Review summarizes the biology of IL-7 and the results of its clinical use that are available so far to provide a perspective on the opportunities for clinical application of this cytokine.
• Immunological biomarkers of tuberculosis
  - Nat Rev Immunol 11(5):343 (2011)
  Currently there are no sufficiently validated biomarkers to aid the evaluation of new tuberculosis vaccine candidates, the improvement of tuberculosis diagnostics or the development of more effective and shorter treatment regimens. To date, the detection of Mycobacterium tuberculosis or its products has not been able to adequately address these needs. Understanding the interplay between the host immune system and M. tuberculosis may provide a platform for the identification of suitable biomarkers, through both unbiased and targeted hypothesis-driven approaches. Here, we review immunological markers, their relation to M. tuberculosis infection stages and their potential use in the fight against tuberculosis.
• Overcoming hurdles in developing successful drugs targeting chemokine receptors
  - Nat Rev Immunol 11(5):355 (2011)
  Chemokines and their receptors are central to the inflammatory process and are attractive therapeutic targets. Drugs that inhibit chemokine receptors are approved for the treatment of HIV infection and for stem cell mobilization, but none have been approved yet for the treatment of inflammatory and/or autoimmune diseases. We analyse the challenges of developing chemokine receptor antagonists, and propose that inappropriate target selection and ineffective dosing, not the 'redundancy' of the chemokine system, are the main barriers to their use as anti-inflammatory therapies. We highlight evidence suggesting that chemokine receptor inhibition will prove to be an effective therapy in inflammatory diseases.