Hot off the presses! Jan 01 Nat Rev Immunol

The Jan 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(1):1 (2011)
  
• Innate immunity: Calling on the neighbours | PDF (171 KB)
  - Nat Rev Immunol 11(1):2 (2011)
  The enteric bacterium Shigella flexneri is known to produce multiple effector proteins that interfere with host cell inflammatory responses. But despite this, infection with this bacterium induces a dramatic inflammatory response, including the secretion of large amounts of CXC-chemokine ligand 8 (CXCL8; also known as IL-8).
• T cells: Shaping Il4 gene expression | PDF (210 KB)
  - Nat Rev Immunol 11(1):3 (2011)
  Transcription of the T helper 2 (TH2)-associated cytokine genes — interleukin-4 (IL4), IL5 and IL13 — is controlled by the TH2 cell master regulator GATA-binding protein 3 (GATA3). However, the molecular basis of GATA3-mediated gene regulation during TH2 cell development is unclear and controversial.
• Innate immunity | Inflammation | MHC molecules | PDF (125 KB)
  - Nat Rev Immunol 11(1):3 (2011)
  Statins enhance formation of phagocyte extracellular traps Chow, O. A.et al. Cell Host Microbe 8, 445–454 (2010)
• Viral immunity: Bad memories | PDF (163 KB)
  - Nat Rev Immunol 11(1):4 (2011)
  Seasonal strains of influenza virus cause more severe disease in infants and the elderly, but historically, pandemic strains of influenza virus have induced the most debilitating disease in healthy young adults. A study in Nature Medicine now offers an explanation for this paradox.
• Innate immunity | Inflammation | Mucosal immunology | PDF (115 KB)
  - Nat Rev Immunol 11(1):4 (2011)
  Plexin-A4–semaphorin 3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm Wen, H.et al. J. Exp. Med.22 Nov 2010 (doi:10.1084/jem.20101138)
• Dendritic cells: pDCs play off scratch | PDF (231 KB)
  - Nat Rev Immunol 11(1):5 (2011)
  Plasmacytoid dendritic cells (pDCs) express Toll-like receptor 7 (TLR7) and TLR9 and produce large amounts of type I interferons (IFNs) in response to viral nucleic acids. However, the contribution of this rare circulating cell population to host immunity remains unclear.
• Regulatory T cells: Kings of the delta blues | PDF (426 KB)
  - Nat Rev Immunol 11(1):6 (2011)
  Regulatory T (TReg) cells prevent excessive inflammatory responses and are crucial for maintaining intestinal homeostasis. Several distinct leukocyte populations are known to be targets of TReg cell-mediated suppression; Sankar Ghosh and colleagues now report that TReg cells can also prevent uncontrolled γδ T cell-mediated attacks against the intestinal microbiota.
• Inflammation: Directions from the matrix | PDF (176 KB)
  - Nat Rev Immunol 11(1):6 (2011)
  Emerging evidence reveals that components of the extracellular matrix can directly regulate inflammatory processes. Now, researchers have identified a role for the matrix component biglycan in the pathogenesis of lupus nephritis through its ability to induce expression of the B cell chemoattractant CXC-chemokine ligand 13 (CXCL13).
• Tumour immunology: CD4+ T cells sponsor oncogene addicts | PDF (191 KB)
  - Nat Rev Immunol 11(1):7 (2011)
  Naturally occurring tumours have multiple and complex genetic abnormalities, but their growth and survival can often be inhibited by the inactivation of a single oncogene. This phenomenon — known as 'oncogene addiction' — can explain the effects of some of our most successful cancer therapeutics, such as the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis).
• B cells: Illuminating the dark zone | PDF (245 KB)
  - Nat Rev Immunol 11(1):8 (2011)
  In a recent paper published in Cell, Dustin, Nussenzweig and colleagues illuminate the dynamics of germinal centre B cell migration and show that T cell help is the limiting factor for the selection of high-affinity B cells.Although much research has focused on defining the mechanisms of B cell selection in germinal centres and the importance of migration between germinal centre dark and light zones, a clear picture of the dynamics of B cell selection in these structures is lacking.
• In the news | PDF (92 KB)
  - Nat Rev Immunol 11(1):8 (2011)
  Most individuals infected with Mycobacterium tuberculosis remain asymptomatic and do not develop tuberculosis, despite the persistent presence of the bacteria. Researchers based in India have discovered a new mechanism that could explain how M. tuberculosis
• Innate immune mechanisms of colitis and colitis-associated colorectal cancer
  - Nat Rev Immunol 11(1):9 (2011)
  The innate immune system provides first-line defences in response to invading microorganisms and endogenous danger signals by triggering robust inflammatory and antimicrobial responses. However, innate immune sensing of commensal microorganisms in the intestinal tract does not lead to chronic intestinal inflammation in healthy individuals, reflecting the intricacy of the regulatory mechanisms that tame the inflammatory response in the gut. Recent findings suggest that innate immune responses to commensal microorganisms, although once considered to be harmful, are necessary for intestinal homeostasis and immune tolerance. This Review discusses recent findings that identify a crucial role for innate immune effector molecules in protection against colitis and colitis-associated colorectal cancer and the therapeutic implications that ensue.
• Imaging techniques for assaying lymphocyte activation in action
  - Nat Rev Immunol 11(1):21 (2011)
  Imaging techniques have greatly improved our understanding of lymphocyte activation. Technical advances in spatial and temporal resolution and new labelling tools have enabled researchers to directly observe the activation process. Consequently, research using imaging approaches to study lymphocyte activation has expanded, providing an unprecedented level of cellular and molecular detail in the field. As a result, certain models of lymphocyte activation have been verified, others have been revised and yet others have been replaced with new concepts. In this article, we review the current imaging techniques that are used to assess lymphocyte activation in different contexts, from whole animals to single molecules, and discuss the advantages and potential limitations of these methods.
• The double life of a B-1 cell: self-reactivity selects for protective effector functions
  - Nat Rev Immunol 11(1):34 (2011)
  During their development, B and T cells with self-reactive antigen receptors are generally deleted from the repertoire to avoid autoimmune diseases. Paradoxically, innate-like B-1 cells in mice are positively selected for self-reactivity and form a pool of long-lived, self-renewing B cells that produce most of the circulating natural IgM antibodies. This Review provides an overview of the developmental processes that shape the B-1 cell pool in mice, outlines the functions of B-1 cells in both the steady state and during host defence, and discusses possible functional B-1 cell homologues that exist in humans.
• Mechanisms for T cell receptor triggering
  - Nat Rev Immunol 11(1):47 (2011)
  There is considerable controversy about the mechanism of T cell receptor (TCR) triggering, the process by which the TCR tranduces signals across the plasma membrane after binding to its ligand (an agonist peptide complexed with an MHC molecule). Three main types of mechanism have been proposed, which involve aggregation, conformational change and segregation. Here, we review recently published evidence for each type of mechanism and conclude that all three may be involved. This complexity may reflect the uniquely demanding nature of TCR-mediated antigen recognition, which requires the detection of a very weak 'signal' (very rare foreign peptide–MHC ligands) in the presence of considerable 'noise' (abundant self peptide–MHC molecules).
• Experimental human challenge infections can accelerate clinical malaria vaccine development
  - Nat Rev Immunol 11(1):57 (2011)
  Malaria is one of the most frequently occurring infectious diseases worldwide, with almost 1 million deaths and an estimated 243 million clinical cases annually. Several candidate malaria vaccines have reached Phase IIb clinical trials, but results have often been disappointing. As an alternative to these Phase IIb field trials, the efficacy of candidate malaria vaccines can first be assessed through the deliberate exposure of participants to the bites of infectious mosquitoes (sporozoite challenge) or to an inoculum of blood-stage parasites (blood-stage challenge). With an increasing number of malaria vaccine candidates being developed, should human malaria challenge models be more widely used to reduce cost and time investments? This article reviews previous experience with both the sporozoite and blood-stage human malaria challenge models and provides future perspectives for these models in malaria vaccine development.
• The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors
  - Nat Rev Immunol 11(1):65 (2011)
  Even before the partial success of a preventive HIV vaccine in a recent Phase III clinical trial, there had been an active research effort to determine one or more immune correlates of protection for HIV infection. This effort has been hampered by the lack of natural protective immunity against HIV. As a result, most of the studies have focused on long-term non-progressive infection or other clinical situations, none of which fully recapitulates protective immunity against HIV. Although this effort has been successful in defining characteristics of T cells in acute and non-progressive HIV infection, and has therefore greatly expanded our knowledge of the immunopathogenesis of AIDS, its success in defining immune correlates of protection is less clear. In this Opinion article we offer a perspective on how successful this effort has been in defining immune correlates of protection that have been, or will be, of use in the development of an HIV vaccine. Our view is that i! nvesting in an iterative approach to human vaccine efficacy trials of sufficient size and sampling frequency will improve the likelihood that an immune correlate of vaccine protection will be defined.