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  • Vigilance or Subversion? Constitutive and Inducible M Cells in Mucosal Tissues
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-22
    David D. Lo

    Microfold (M) cells are epithelial cells present in mucosal tissues and specialized for the capture of luminal microparticles and their delivery to underlying immune cells; thus, they are crucial participants in mucosal immune surveillance. Multiple phenotypic subsets of M cells have now been described, all sharing a unique apical morphology that provides clues to their ability to capture microbial particles. The existence of diverse M cell phenotypes, especially inflammation-inducible M cells, provides an intriguing puzzle: some variants may augment luminal surveillance to boost mucosal immunity, while others may promote microbial access to tissues. Here, I consider the unique induction requirements of each M cell subset and functional differences, highlighting the potentially distinct consequences in mucosal immunity.

    更新日期:2017-09-23
  • Vigilance or Subversion? Constitutive and Inducible M Cells in Mucosal Tissues
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-22
    David D. Lo
    更新日期:2017-09-23
  • Beyond Chemoattraction: Multifunctionality of Chemokine Receptors in Leukocytes
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-18
    Pilar López-Cotarelo, Carolina Gómez-Moreira, Olga Criado-García, Lucas Sánchez, José Luis Rodríguez-Fernández

    The word chemokine is a combination of the words chemotactic and cytokine, in other words cytokines that promote chemotaxis. Hence, the term chemokine receptor refers largely to the ability to regulate chemoattraction. However, these receptors can modulate additional leukocyte functions, as exemplified by the case of CCR7 which, apart from chemotaxis, regulates survival, migratory speed, endocytosis, differentiation and cytoarchitecture. We present evidence highlighting that multifunctionality is a common feature of chemokine receptors. Based on the activities that they regulate, we suggest that chemokine receptors can be classified into inflammatory (which control both inflammatory and homeostatic functions) and homeostatic families. The information accrued also suggests that the non-chemotactic functions controlled by chemokine receptors may contribute to optimizing leukocyte functioning under normal physiological conditions and during inflammation.

    更新日期:2017-09-20
  • Control of Immune Cell Homeostasis and Function by lncRNAs
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-15
    Walter K. Mowel, Jonathan J. Kotzin, Sam J. McCright, Vanessa D. Neal, Jorge Henao-Mejia

    The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues. We review here how lncRNAs control the function and homeostasis of cell populations during immune responses, emphasizing the diverse molecular mechanisms by which lncRNAs tune highly contextualized transcriptional programs. In addition, we discuss the new challenges faced in interrogating lncRNA mechanisms and function in the immune system.

    更新日期:2017-09-20
  • Common Senses
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-13
    Jacques Deguine

    Taste. Sight. Touch. Smell. Hearing. That M. Night Shyamalan movie. While the list has now grown far beyond those, we still associate senses with nervous systems, and by extension animals. Yet, any immune response, in any organism, must begin with the recognition of a threat, and properly calibrated immune ‘senses’ are critical to the avoidance of autoimmunity. This sense of self and non-self was originally thought to be encoded in the selection of adaptive cells. However, Charles Janeway in 1989 and Polly Matzinger in 1994 moved the field forward by introducing the notion of the innate sensing of molecular patterns characteristic of pathogens and cellular damage, respectively, as critical immune gatekeepers.

    更新日期:2017-09-20
  • Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-12
    Mohan S Maddur, Srini V. Kaveri, Jagadeesh Bayry

    Intravenous immunoglobulin (IVIG), a pooled normal IgG formulation prepared from thousands of healthy donors’ plasma, is extensively used for the immunotherapy of autoimmune and inflammatory disorders. Recent reports demonstrate that IVIG exerts anti-inflammatory actions by stimulating the activation and expansion of regulatory T (Treg) cells by multiple mechanisms via antigen-presenting cells (APCs).

    更新日期:2017-09-20
  • Metabolic Links between Plasma Cell Survival, Secretion, and Stress
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-11
    Wing Y. Lam, Deepta Bhattacharya

    Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy. Many of these processes are likely to be linked, thereby affording possibilities to improve vaccine design and to develop new therapies for autoimmunity. We review here aspects of plasma cell biology with an emphasis on recent studies and the relationships between intermediary metabolism, antibody production, and lifespan.

    更新日期:2017-09-20
  • Mitochondrial Dynamics at the Interface of Immune Cell Metabolism and Function
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-09
    Angelika S. Rambold, Erika L. Pearce

    Immune cell differentiation and function are crucially dependent on specific metabolic programs dictated by mitochondria, including the generation of ATP from the oxidation of nutrients and supplying precursors for the synthesis of macromolecules and post-translational modifications. The many processes that occur in mitochondria are intimately linked to their morphology that is shaped by opposing fusion and fission events. Exciting evidence is now emerging that demonstrates reciprocal crosstalk between mitochondrial dynamics and metabolism. Metabolic cues can control the mitochondrial fission and fusion machinery to acquire specific morphologies that shape their activity. We review the dynamic properties of mitochondria and discuss how these organelles interlace with immune cell metabolism and function.

    更新日期:2017-09-20
  • Tissue-Specific Immunity at the Oral Mucosal Barrier
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-09
    Niki M. Moutsopoulos, Joanne E. Konkel

    The oral mucosal barrier is constantly exposed to a plethora of triggers requiring immune control, including a diverse commensal microbiome, ongoing damage from mastication, and dietary and airborne antigens. However, how these tissue-specific cues participate in the training of immune responsiveness at this site is minimally understood. Moreover, the mechanisms mediating homeostatic immunity at this interface are not yet fully defined. Here we present basic aspects of the oral mucosal barrier and discuss local cues that may modulate and train local immune responsiveness. We particularly focus on the immune cell network mediating immune surveillance at a specific oral barrier, the gingiva – a constantly stimulated and dynamic environment where homeostasis is often disrupted, resulting in the common inflammatory disease periodontitis.

    更新日期:2017-09-20
  • DNA Sensing across the Tree of Life
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-05
    Stefania Gallucci, Massimo E. Maffei

    From plants to mammals, pattern recognition receptors (PRRs) specifically recognize DNA, as a potential marker of either infection or damage. These receptors play critical roles in inflammation, immunity, and pathogen resistance. Importantly, given the ubiquity of DNA, its sensing must be tightly regulated. DNA localization plays a key role in recognition, as highlighted by Toll-like receptor 9 (TLR9) in the endosomal compartment and cyclic GMP–AMP synthase (cGAS) and absent in melanoma 2 (AIM2) in the cytoplasm. Sequence and structure also enhance recognition across species. Evidence in plants supports the sensing of extracellular DNA by PRRs, leading to calcium-dependent signaling, although no receptor has been definitively identified yet. Here, we review the shared and distinct features of DNA sensors, and their physiological functions, across the tree of life.

    更新日期:2017-09-20
  • Understanding Immunity through the Lens of Disease Ecology
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-04
    Stephen M. Hedrick

    As we describe the immune system in ever more exquisite detail, we might find that no matter how successful, this approach will not be sufficient to understand the spread of infectious agents, their susceptibility to vaccine therapy, and human disease resistance. Compared with the strict reductionism practiced as a means of characterizing most biological processes, I propose that the progression and outcome of disease-causing host–parasite interactions will be more clearly understood through a focus on disease ecology.

    更新日期:2017-09-20
  • From Original Antigenic Sin to the Universal Influenza Virus Vaccine
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-01
    Carole Henry, Anna-Karin E. Palm, Florian Krammer, Patrick C. Wilson

    Antibody responses are essential for protection against influenza virus infection. Humans are exposed to a multitude of influenza viruses throughout their lifetime and it is clear that immune history influences the magnitude and quality of the antibody response. The ‘original antigenic sin’ concept refers to the impact of the first influenza virus variant encounter on lifelong immunity. Although this model has been challenged since its discovery, past exposure, and likely one’s first exposure, clearly affects the epitopes targeted in subsequent responses. Understanding how previous exposure to influenza virus shapes antibody responses to vaccination and infection is critical, especially with the prospect of future pandemics and for the effective development of a universal influenza vaccine.

    更新日期:2017-09-20
  • The Multifaceted Personality of Intestinal CX3CR1+ Macrophages
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-24
    Mari Regoli, Eugenio Bertelli, Massimo Gulisano, Claudio Nicoletti

    Intestinal macrophages expressing the fraktalkine receptor (CX3CR1+) represent a cell population that plays a variety of roles ranging from maintaining intestinal immune homeostasis at steady state to controlling antigen access by extending transepithelial dendrites (TEDs) to capture luminal microbes and shuttle them across the epithelium to initiate immune responses. However, recent evidence shows that very early during infection, pathogen-capturing CX3CR1+macrophages migrate to the lumen of the small intestine, therefore preventing pathogens from traversing the epithelium. Here we discuss the complexity of the at-times seemingly opposing roles played by these cells and propose that CX3CR1-mediated pathogen exclusion is part of a defensive strategy against infections that includes multiple effector mechanisms acting synergistically at the intestinal mucosa.

    更新日期:2017-09-20
  • Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-22
    Monika Fleshner, Camille R. Crane

    Psychological/physical stressors and local tissue damage increase inflammatory proteins in tissues and blood in humans and animals, in the absence of pathogenic disease. Stress-evoked cytokine/chemokine responses, or sterile inflammation, can facilitate host survival and/or negatively affect health, depending on context. Recent evidence supports the hypothesis that systemic stress-evoked sterile inflammation is initiated by the sympathetic nervous system, resulting in the elevation of exosome-associated immunostimulatory endogenous danger/damage associated molecular patterns (DAMPs) and a reduction in immunoinhibitory miRNA, which are carried in the circulation to tissues throughout the body. We propose that sterile inflammation should be considered an elemental feature of the stress response and that circulating exosomes transporting immunomodulatory signals, may play a role fundamental role in immune homeostasis.

    更新日期:2017-09-20
  • cGAS–STING and Cancer: Dichotomous Roles in Tumor Immunity and Development
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-19
    Kevin W. Ng, Erin A. Marshall, John C. Bell, Wan L. Lam

    cGMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) sensing has emerged as a key regulator of innate immune responses to both exogenous and endogenous DNA. Recent studies reveal critical roles for this pathway in natural antitumor immunity across cancer types as well as in immune checkpoint blockade therapy. However, it is also clear that some tumors evade cGAS–STING-mediated immune responses, and immunomodulatory therapeutics are currently being explored to target this pathway. Finally, we also discuss recent observations that cGAS–STING-mediated inflammation may promote tumor initiation, growth, and metastasis in certain malignancies and how this may complicate the utility of this pathway in therapeutic development.

    更新日期:2017-09-20
  • Post-Translational Peptide Splicing and T Cell Responses
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-19
    Michele Mishto, Juliane Liepe

    CD8+T cell specificity depends on the recognition of MHC class I–epitope complexes at the cell surface. These epitopes are mainly produced via degradation of proteins by the proteasome, generating fragments of the original sequence. However, it is now clear that proteasomes can produce a significant portion of epitopes by reshuffling the antigen sequence, thus expanding the potential antigenic repertoire. MHC class I-restricted spliced epitopes have been described in tumors and infections, suggesting an unpredicted relevance of these peculiar peptides. We review current knowledge about proteasome-catalyzed peptide splicing (PCPS), the emerging rules governing this process, and the potential implications for our understanding and therapeutic use of CD8+T cells, as well as mechanisms generating other non-canonical antigenic epitopes targeted by the T cell response.

    更新日期:2017-09-20
  • The Mechanisms of T Cell Selection in the Thymus
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-19
    Hiroyuki Takaba, Hiroshi Takayanagi

    T cells undergo positive and negative selection in the thymic cortex and medulla, respectively. A promiscuous expression of a wide array of self-antigens in the thymus is essential for the negative selection of self-reactive T cells and the establishment of central tolerance. Aire was originally thought to be the exclusive factor regulating the expression of tissue-restricted antigens, but Fezf2 recently emerged as a critical transcription factor in this regulatory activity. Fezf2 is selectively expressed in thymic medullary epithelial cells, regulates a large number of tissue-restricted antigens and suppresses the onset of autoimmune responses. Here, we discuss novel findings on the transcriptional mechanisms of tissue restricted-antigen expression in the medullary thymic epithelial cells and its effects on T cell selection.

    更新日期:2017-09-20
  • Mechanisms of Mixed Chimerism-Based Transplant Tolerance
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-18
    Julien Zuber, Megan Sykes

    Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation (BMT) with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism such protocols can permit central deletional tolerance, but with a significant risk of graft-versus-host (GVH) disease (GVHD). By contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells (Tregs) followed by gradual, presumably peripheral, clonal deletion of donor-reactive T cells. Here we review recent mechanistic insights into tolerance and the development of more robust and safer protocols for tolerance induction that will be guided by innovative immune monitoring tools.

    更新日期:2017-09-20
  • Dendritic Cells As Inducers of Peripheral Tolerance
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-18
    Courtney A. Iberg, Andrew Jones, Daniel Hawiger

    Mechanisms of tolerance initiated in the thymus are indispensable for establishing immune homeostasis, but they may not be sufficient to prevent tissue-specific autoimmune diseases. In the periphery, dendritic cells (DCs) play a crucial tolerogenic role, extending the maintenance of immune homeostasis and blocking autoimmune responses. We review here these essential roles of DCs in orchestrating mechanisms of peripheral T cell tolerance as determined by targeted delivery of defined antigens to DCsin vivoin combination with various genetic modifications of DCs. Further, we discuss how DC functions empowered by specific delivery of T cell antigens could be harnessed for tolerance induction in clinical settings.

    更新日期:2017-09-20
  • Do Type I Interferons Link Systemic Autoimmunities and Metabolic Syndrome in a Pathogenetic Continuum?
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-17
    Dipyaman Ganguly

    The central pathogenetic role of type I interferons (IFNs) in several systemic autoimmune diseases is well established. Recent studies have also discovered a similar crucial role of type I IFNs in different components of metabolic disorders. Self nucleic acid-driven Toll-like receptor (TLR) activation in plasmacytoid dendritic cells (pDCs) and type I IFN induction appear to be the key initiating events shared by most of these autoimmune and metabolic diseases. Further strengthening this link, many patients with systemic autoimmunities also present with metabolic disorders. This concurrence of autoimmunities and metabolic disorders may be explained by a single pathogenetic continuum, and suggests shared targets for potential new therapies.

    更新日期:2017-09-20
  • NOD1 and NOD2: Beyond Peptidoglycan Sensing
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-16
    A. Marijke Keestra-Gounder, Renée M. Tsolis

    NOD1 and NOD2 are pattern recognition receptors of the innate immune system with well-established roles in sensing fragments of bacterial peptidoglycan. In addition to their role as microbial sensors, recent evidence indicates that nucleotide-binding oligomerization domains (NODs) can also recognize a broader array of danger signals. Indeed, recent work has expanded the roles of NOD1 and NOD2 to encompass not only sensing of infections with viruses and parasites but also perceiving perturbations of cellular processes such as regulation of the actin cytoskeleton and maintenance of endoplasmic reticulum homeostasis. This review will comment on recent progress and point out emerging questions in these areas.

    更新日期:2017-09-20
  • TRIM21 and the Function of Antibodies inside Cells
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-11
    David A. Rhodes, David A. Isenberg

    Therapeutic antibodies targeting disease-associated antigens are key tools in the treatment of cancer and autoimmunity. So far, therapeutic antibodies have targeted antigens that are, or are presumed to be, extracellular. A largely overlooked property of antibodies is their functional activity inside cells. The diverse literature dealing with intracellular antibodies emerged historically from studies of the properties of some autoantibodies. The identification of tripartite motif (TRIM) 21 as an intracellular Fc receptor linking cytosolic antibody recognition to the ubiquitin proteasome system brings this research into sharper focus. We review critically the research related to intracellular antibodies, link this to the TRIM21 effector mechanism, and highlight how this work is exposing the previously restricted intracellular space to the potential of therapeutic antibodies.

    更新日期:2017-09-20
  • Neutrophilic Inflammation in Asthma and Association with Disease Severity
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-04
    Anuradha Ray, Jay K. Kolls

    Asthma is a chronic inflammatory disorder of the airways. While the local infiltration of eosinophils and mast cells, and their role in the disease have long been recognized, neutrophil infiltration has also been assessed in many clinical studies. In these studies, airway neutrophilia was associated with asthma severity. Importantly, neutrophilia also correlates with asthma that is refractory to corticosteroids, the mainstay of asthma treatment. However, it is now increasingly recognized that neutrophils are a heterogeneous population, and a more precise phenotyping of these cells may help delineate different subtypes of asthma. Here, we review current knowledge of the role of neutrophils in asthma and highlight future avenues of research in this field.

    更新日期:2017-09-20
  • Tonic Signals: Why Do Lymphocytes Bother?
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-25
    Darienne R. Myers, Julie Zikherman, Jeroen P. Roose

    Since the 1990s it has been known that B and T lymphocytes exhibit low-level, constitutive signaling in the basal state (tonic signaling). These lymphocytes display a range of affinity for self, which in turn generates a range of tonic signaling. Surprisingly, what signaling pathways are active in the basal state and the functional relevance of the observed tonic signaling heterogeneity remain open questions today. Here we summarize what is known about the mechanistic and functional details of tonic signaling. We highlight recent advances that have increased our understanding of how the amount of tonic signal impacts immune function, describing novel tools that have moved the field forward and toward a molecular understanding of tonic signaling.

    更新日期:2017-09-20
  • Programmed Cell Death and Inflammation: Winter Is Coming
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-19
    Joseph P. Kolb, Thomas H. Oguin, Andrew Oberst, Jennifer Martinez

    The life of an organism requires the assistance of an unlikely process: programmed cell death. Both development and the maintenance of homeostasis result in the production of superfluous cells that must eventually be disposed of. Furthermore, programmed cell death can also represent a defense mechanism; for example, by depriving pathogens of a replication niche. The responsibility of handling these dead cells falls on phagocytes of the immune system, which surveil their surroundings for dying or dead cells and efficiently clear them in a quiescent manner. This process, termed efferocytosis, depends on cooperation between the phagocyte and the dying cell. In this review we explore different types of programmed cell death and their impact on innate immune responses.

    更新日期:2017-09-20
  • Langerhans Cells – The Macrophage in Dendritic Cell Clothing
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-15
    Thomas Doebel, Benjamin Voisin, Keisuke Nagao

    Our assumptions on the identity and functions of Langerhans cells (LCs) of the epidermis have undergone considerable changes. Once thought to be prototypic representatives of the dendritic cell (DC) lineage, they are now considered to be a specialized subset of tissue-resident macrophages. Despite this, LCs display a remarkable mixture of properties. Like many tissue macrophages, they self-maintain locally. However, unlike tissue macrophages and similar to DCs, they homeostatically migrate to lymph nodes and present antigen to antigen-specific T cells. Current evidence indicates that the immune responses initiated by LCs are complex and dependent on antigenic properties and localization of the stimulus. This complexity is reflected in the recently demonstrated roles of LCs in type 17, regulatory, and humoral immune responses.

    更新日期:2017-09-20
  • Regulation of the Immune System by Laminins
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-03
    Thomas Simon, Jonathan S. Bromberg

    Laminins are trimeric proteins that are major components of the basement membranes that separate endothelia and epithelia from the underlying tissue. Sixteen laminin isoforms have been described, each with distinct tissue expression patterns and functions. While laminins have a critical structural role, recent evidence also indicates that they also impact the migration and functions of immune cells. Laminins are differentially expressed upon immunity or tolerance and orientate the immune response. This review will summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system. Finally, the role of the laminins in autoimmune diseases and transplantation will be discussed.

    更新日期:2017-09-20
  • Dying for a Cause: Regulated Necrosis of Tissue-Resident Macrophages upon Infection
    Trends Immunol. (IF 13.287) Pub Date : 2017-06-19
    Florent Ginhoux, Camille Bleriot, Marc Lecuit

    We celebrated in 2016 the centenary of the death of Ilya Ilitch Metchnikov (1845–1916), the founding father of innate immunology. His studies on the description of macrophages, their phagocytic function, and their key role in eliminating microbes were recognized by the Nobel Prize in Physiology and Medicine, and constitute a cornerstone of immunology (https://www.nobelprize.org/nobel_prizes/medicine/laureates/1908/mechnikov-facts.html). Since then, macrophages are typically considered as tissue scavengers, that capture and destroy microbial intruders, thereby ensuring tissue protection and host defense against infections.

    更新日期:2017-09-20
  • Evolutionary Convergence and Divergence in NLR Function and Structure
    Trends Immunol. (IF 13.287) Pub Date : 2017-05-31
    Etienne Meunier, Petr Broz

    The recognition of cellular damage caused by either pathogens or abiotic stress is essential for host defense in all forms of life in the plant and animal kingdoms. The NOD-like receptors (NLRs) represent a large family of multidomain proteins that were initially discovered for their role in host defense in plants and vertebrates. Over recent years the wide distribution of NLRs among metazoans has become apparent and their origins have begun to emerge. Moreover, intense study of NLR function has shown that they play essential roles beyond pathogen recognition – in the regulation of antigen presentation, cell death, inflammation, and even in embryonic development. We summarize here the latest insights into NLR biology and discuss examples of converging and diverging evolution of NLR function and structure.

    更新日期:2017-09-20
  • Lipopolysaccharide Detection across the Kingdoms of Life
    Trends Immunol. (IF 13.287) Pub Date : 2017-05-24
    Jonathan C. Kagan

    Studies in recent years have uncovered a diverse set of eukaryotic receptors that recognize lipopolysaccharide (LPS), the major outer-membrane component of Gram-negative bacteria. Indeed, Toll-like receptors, G-protein-coupled receptors, integrins, receptor-like kinases, and caspases have emerged as important LPS-interacting proteins. In this review, the mammalian receptors that detect LPS are described. I highlight how no host protein is involved in all LPS responses, but a single lipid (phosphatidylinositol-4,5-bisphosphate) regulates many LPS responses, including endocytosis, phagocytosis, inflammation, and pyroptosis. I further describe LPS response systems that operate specifically in plants, and discuss potentially new LPS response systems that await discovery. This diversity of receptors for a single microbial product underscores the importance of host–microbe interactions in multiple kingdoms of life.

    更新日期:2017-09-20
  • Evolutionary Origins of cGAS-STING Signaling
    Trends Immunol. (IF 13.287) Pub Date : 2017-04-14
    Shally R. Margolis, Stephen C. Wilson, Russell E. Vance

    Detection of foreign nucleic acids is an important strategy for innate immune recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger cGAMP to activate the signaling adaptor STING. While induction of antiviral type I interferons (IFNs) is the major outcome of STING activation in vertebrates, it has recently become clear that core components of the cGAS-STING pathway evolved more than 600 million years ago, predating the evolution of type I IFNs. Here we discuss the evolutionary origins of the cGAS-STING pathway, and consider the possibility that the ancestral functions of STING may have included activation of antibacterial immunity.

    更新日期:2017-09-20
  • The S(c)ensory Immune System Theory
    Trends Immunol. (IF 13.287) Pub Date : 2017-03-07
    Henrique Veiga-Fernandes, António A. Freitas

    Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms. This context determined the emergence of the ‘sensory immune system’, which operates in a s(c)ensor mode to ensure systems physiology, organismic homeostasis, and perpetuation of its replicating molecules.

    更新日期:2017-09-20
  • Beyond Chemoattraction: Multifunctionality of Chemokine Receptors in Leukocytes
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-18
    Pilar López-Cotarelo, Carolina Gómez-Moreira, Olga Criado-García, Lucas Sánchez, José Luis Rodríguez-Fernández
    更新日期:2017-09-20
  • Control of Immune Cell Homeostasis and Function by lncRNAs
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-15
    Walter K. Mowel, Jonathan J. Kotzin, Sam J. McCright, Vanessa D. Neal, Jorge Henao-Mejia
    更新日期:2017-09-20
  • Common Senses
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-13
    Jacques Deguine

    Taste. Sight. Touch. Smell. Hearing. That M. Night Shyamalan movie. While the list has now grown far beyond those, we still associate senses with nervous systems, and by extension animals. Yet, any immune response, in any organism, must begin with the recognition of a threat, and properly calibrated immune ‘senses’ are critical to the avoidance of autoimmunity. This sense of self and non-self was originally thought to be encoded in the selection of adaptive cells. However, Charles Janeway in 1989 and Polly Matzinger in 1994 moved the field forward by introducing the notion of the innate sensing of molecular patterns characteristic of pathogens and cellular damage, respectively, as critical immune gatekeepers.

    更新日期:2017-09-20
  • Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-12
    Mohan S Maddur, Srini V. Kaveri, Jagadeesh Bayry
    更新日期:2017-09-20
  • Metabolic Links between Plasma Cell Survival, Secretion, and Stress
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-11
    Wing Y. Lam, Deepta Bhattacharya
    更新日期:2017-09-20
  • Mitochondrial Dynamics at the Interface of Immune Cell Metabolism and Function
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-09
    Angelika S. Rambold, Erika L. Pearce
    更新日期:2017-09-20
  • Tissue-Specific Immunity at the Oral Mucosal Barrier
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-09
    Niki M. Moutsopoulos, Joanne E. Konkel
    更新日期:2017-09-20
  • DNA Sensing across the Tree of Life
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-05
    Stefania Gallucci, Massimo E. Maffei
    更新日期:2017-09-20
  • Understanding Immunity through the Lens of Disease Ecology
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-04
    Stephen M. Hedrick
    更新日期:2017-09-20
  • From Original Antigenic Sin to the Universal Influenza Virus Vaccine
    Trends Immunol. (IF 13.287) Pub Date : 2017-09-01
    Carole Henry, Anna-Karin E. Palm, Florian Krammer, Patrick C. Wilson
    更新日期:2017-09-20
  • The Multifaceted Personality of Intestinal CX3CR1+ Macrophages
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-24
    Mari Regoli, Eugenio Bertelli, Massimo Gulisano, Claudio Nicoletti
    更新日期:2017-09-20
  • Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-22
    Monika Fleshner, Camille R. Crane
    更新日期:2017-09-20
  • cGAS–STING and Cancer: Dichotomous Roles in Tumor Immunity and Development
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-19
    Kevin W. Ng, Erin A. Marshall, John C. Bell, Wan L. Lam
    更新日期:2017-09-20
  • Post-Translational Peptide Splicing and T Cell Responses
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-19
    Michele Mishto, Juliane Liepe
    更新日期:2017-09-20
  • The Mechanisms of T Cell Selection in the Thymus
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-19
    Hiroyuki Takaba, Hiroshi Takayanagi
    更新日期:2017-09-20
  • Mechanisms of Mixed Chimerism-Based Transplant Tolerance
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-18
    Julien Zuber, Megan Sykes
    更新日期:2017-09-20
  • Dendritic Cells As Inducers of Peripheral Tolerance
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-18
    Courtney A. Iberg, Andrew Jones, Daniel Hawiger
    更新日期:2017-09-20
  • Do Type I Interferons Link Systemic Autoimmunities and Metabolic Syndrome in a Pathogenetic Continuum?
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-17
    Dipyaman Ganguly
    更新日期:2017-09-20
  • NOD1 and NOD2: Beyond Peptidoglycan Sensing
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-16
    A. Marijke Keestra-Gounder, Renée M. Tsolis
    更新日期:2017-09-20
  • TRIM21 and the Function of Antibodies inside Cells
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-11
    David A. Rhodes, David A. Isenberg
    更新日期:2017-09-20
  • Neutrophilic Inflammation in Asthma and Association with Disease Severity
    Trends Immunol. (IF 13.287) Pub Date : 2017-08-04
    Anuradha Ray, Jay K. Kolls
    更新日期:2017-09-20
  • Environments Tune and Select Cellular Diversity
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-31
    Brian A. Kidd
    更新日期:2017-09-20
  • Tonic Signals: Why Do Lymphocytes Bother?
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-25
    Darienne R. Myers, Julie Zikherman, Jeroen P. Roose
    更新日期:2017-09-20
  • MHC Class I Cross-Presentation: Stage Lights on Sec22b
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-22
    Sebastian Montealegre, Peter van Endert

    Efficient (cross-)presentation of antigens internalized by dendritic cells (DCs) requires vesicular communication between the early secretory and the endocytic/phagocytic pathways, in which the Sec22b protein has been suggested to have a key role. Here, we undertake a critical assessment of two new studies that evaluate the role of Sec22b using gene-targeted mice and come to contradictory conclusions.

    更新日期:2017-09-20
  • Programmed Cell Death and Inflammation: Winter Is Coming
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-19
    Joseph P. Kolb, Thomas H. Oguin, Andrew Oberst, Jennifer Martinez
    更新日期:2017-09-20
  • Langerhans Cells – The Macrophage in Dendritic Cell Clothing
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-15
    Thomas Doebel, Benjamin Voisin, Keisuke Nagao
    更新日期:2017-09-20
  • The Ambiguous Role of γδ T Lymphocytes in Antitumor Immunity
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-11
    Guranda Chitadze, Hans-Heinrich Oberg, Daniela Wesch, Dieter Kabelitz
    更新日期:2017-09-20
  • THEMIS: Two Models, Different Thresholds
    Trends Immunol. (IF 13.287) Pub Date : 2017-07-08
    Seeyoung Choi, Richard Cornall, Renaud Lesourne, Paul E. Love
    更新日期:2017-09-20
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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