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Current Opinion in Immunology

Eline Haspeslagh, Ines Heyndrickx, Hamida Hammad, Bart N Lambrecht
The hygiene hypothesis was initially proposed as an explanation for the alarming rise in allergy prevalence in the last century. The immunological idea behind this hypothesis was a lack of infections associated with a Western lifestyle and a consequential reduction in type 1 immune responses. It is now understood that the development of tolerance to allergens depends on microbial colonization and immunostimulatory environmental signals during early-life or passed on by the mother. These environmental cues are sensed and integrated by barrier epithelial cells of the lungs and possibly skin, which in turn instruct dendritic cells to regulate or impede adaptive T cell responses...
July 6, 2018: Current Opinion in Immunology
Jörn Coers, Hailey M Brown, Seungmin Hwang, Gregory A Taylor
Once pathogens have breached the mechanical barriers to infection, survived extracellular immunity and successfully invaded host cells, cell-intrinsic immunity becomes the last line of defense to protect the mammalian host against viruses, bacteria, fungi and protozoa. Many cell-intrinsic defense programs act as high-precision weapons that specifically target intracellular microbes or cytoplasmic sites of microbial replication while leaving endogenous organelles unharmed. Critical executioners of cell-autonomous immunity include interferon-inducible dynamin-like GTPases and autophagy proteins, which often act cooperatively in locating and antagonizing intracellular pathogens...
July 5, 2018: Current Opinion in Immunology
Pascal Gasser, Alexander Eggel
Immunoglobulin E (IgE) represents the least abundant antibody isotype in human serum. Nevertheless, it has the ability to induce potent allergic reactions. As a key component in the development and manifestation of hypersensitivity responses against usually non-hazardous foreign substances, IgE has become a major target of investigation and the subject of multiple therapeutic approaches for the treatment of allergies. Recent advances in the understanding of pathophysiologic mechanisms underlying IgE-associated allergic disorders have led to the generation of new drug candidates that are currently in development or under clinical evaluation...
July 4, 2018: Current Opinion in Immunology
Tate Michelle D, Mansell Ashley
Inflammation is an integral aspect of influenza A virus (IAV) infection. It is critical to induce an antiviral environment to reduce viral replication and dissemination, while also being essential to the development and maturation of adaptive immunity, which ultimately resolves infection. Conversely, excessive pulmonary inflammation and cellular influx are characteristic of lethal IAV infections. It has become increasingly apparent that the innate immune inflammasome complex is a crucial moderator in IAV disease pathogenesis...
June 30, 2018: Current Opinion in Immunology
Masato Kubo
Mast cells and basophils have similar characteristics in terms of their function and development. They both have detrimental functions, being implicated in pro-inflammatory responses to allergens, but can also provide protection against multicellular parasites such as parasitic worms (helminths). Both cell types express the high affinity Fc receptor for IgE, FcεRI, and allergen cross-linking of this receptor triggers degranulation and release a set of cytokines and biochemical mediators. Although mast cells and basophils are similar in many respects, newly developed antibody reagents and genetically modified mouse models that enable cell type-specific deletion have allowed us to appreciate their independent in vivo roles...
June 28, 2018: Current Opinion in Immunology
David J Topham, Phuong Nguyen, Mark Y Sangster
The emergence of avian influenza viruses stimulated pandemic concerns and efforts to develop protective vaccines. Studies of the immune responses to experimental vaccines for pandemic influenza have taught us lessons about human immunity to influenza in general that can be applied to seasonal, pandemic, and even universal vaccine responses. For example, the concepts of targeting the hemagglutinin stalk and elicitation of stalk reactive antibodies grew out of studies of the 2009 pandemic H1N1 vaccines. More recently, the phenomenon of imprinting, the influence of early life exposure to influenza modifying responses to the viruses or vaccines later in life, has been reinforced through the study of potential pandemic influenza virus vaccines such as H7N9...
June 26, 2018: Current Opinion in Immunology
Liam B King, Brandyn R West, Sharon L Schendel, Erica Ollmann Saphire
Filoviruses, including ebolaviruses and marburgviruses, are the causative agents of highly lethal disease outbreaks. The 2013-2016 Ebola virus outbreak was responsible for >28000 infections and >11000 deaths. Although there are currently no licensed vaccines or therapeutics for any filovirus-induced disease, monoclonal antibodies (mAbs) are among the most promising options for therapeutic development. Hundreds of mAbs have been isolated from human survivors of filovirus infections that target the viral spike glycoprotein (GP)...
June 22, 2018: Current Opinion in Immunology
Jennifer R Honda, Scott Alper, Xiyuan Bai, Edward D Chan
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and human exposure is likely to be pervasive; yet, the occurrence of NTM-related diseases is relatively infrequent. This discrepancy suggests that host risk factors play an integral role in vulnerability to NTM infections. Isolated NTM lung disease (NTM-LD) is often due to underlying anatomical pulmonary or immune disorders, either of which may be acquired or genetic. However, many cases of NTM-LD have no known underlying risk factors and may be multigenic and/or multicausative...
June 21, 2018: Current Opinion in Immunology
Anna M Trier, Brian S Kim
Atopic dermatitis (AD) is an inflammatory skin disease characterized by two primary features: relapsing skin lesions and chronic itch. Major advances in our understanding of type 2 immunity have led to new insights into the critical factors that promote the development and persistence of AD-associated skin inflammation. Although inflammation is strongly associated with the development of atopic itch, the precise mechanisms by which itch arises in AD are poorly understood. In this review, we highlight recent studies that have started to unveil how various proinflammatory factors released within the skin can elicit sensations of itch and discuss the therapeutic potential of targeting these neuroimmunologic processes...
June 20, 2018: Current Opinion in Immunology
Nicholas D Peterson, Read Pukkila-Worley
New classes of antimicrobials that are effective therapies for infections with multi-drug resistant pathogens are urgently needed. The nematode Caenorhabditis elegans has been incorporated into small molecule screening platforms to identify anti-infective compounds that provide protection of a host during infection. The use of a live animal in these screening systems offers several advantages, including the ability to identify molecules that boost innate immune responses in a manner advantageous to host survival and compounds that disrupt bacterial virulence mechanisms...
June 20, 2018: Current Opinion in Immunology
Melanie Schirmer, Vinod Kumar, Mihai G Netea, Ramnik J Xavier
Cytokines are important cell-signaling molecules that activate and modulate immune responses. Major factors influencing cytokine variation in healthy individuals are host genetics, non-heritable factors and the microbiome. Genetic variation accounts for a significant part of heterogeneity in cytokine production by peripheral blood mononuclear cells. Variation in cytokines such as IL-6 and IL-6Ra is strongly influenced by heritability, suggesting an evolutionarily pressure for their genetic regulation that potentially contributes to differences in immune responsiveness between human populations...
June 15, 2018: Current Opinion in Immunology
Colleen M Lau, Joseph C Sun
Immunological memory is broadly understood as the underlying mechanism by which an organism remembers previous encounters with pathogens, aberrant cells, or self-antigens to produce a more rapid or robust secondary response upon re-encounter. This phenomenon is widely accepted as the hallmark feature of the adaptive immune system. However, work within the last decade has continuously challenged this viewpoint and opened up the idea that immunological memory extends beyond just conventional B cells and T cells...
June 11, 2018: Current Opinion in Immunology
Jenna J Guthmiller, Patrick C Wilson
Individuals are exposed to influenza viruses throughout their lifetime. Accumulating evidence shows the first viruses an individual is exposed to leaves an imprint on the antibody response induced by subsequent drifted and novel influenza viral exposures. Imprinted humoral immunity against influenza viruses relies on biased immune memory to influenza viruses for which memory B cell responses were initially generated against. Imprinting allows for antibodies to adapt to drifted influenza viruses while maintaining binding potential for the first influenza viruses an individual is exposed to...
June 8, 2018: Current Opinion in Immunology
William J Crisler, Laurel L Lenz
Type I and type II interferons (IFNα/β and IFNγ) are cytokines that play indispensable roles in directing myeloid cell activity during inflammatory and immune responses. Each IFN type binds a distinct receptor (IFNAR or IFNGR) to transduce signals that reshape gene expression and function of myeloid and other cell types. In the context of murine models and human bacterial infections, production of IFNγ generally promotes resistance while production of IFNα/β is associated with increased host susceptibility...
June 7, 2018: Current Opinion in Immunology
Coraline Radermecker, Renaud Louis, Fabrice Bureau, Thomas Marichal
The contribution of neutrophils to asthma pathogenesis has been mainly studied in the context of non-allergic neutrophilic asthma. However, neutrophils can also be rapidly recruited and are largely present in the airways of allergic eosinophilic asthmatic patients. Under these circumstances, they possess specific phenotypic features distinguishing them from resting blood neutrophils and are endowed with particular functions. The exact contribution of neutrophils to allergic asthma pathogenesis is still unclear, but growing experimental evidence supports the ability of neutrophils or neutrophil-derived products to influence the underlying allergic type 2 immune response and cardinal features of allergic asthma, thus shedding new light on neutrophil biology and functions in an allergic context...
June 5, 2018: Current Opinion in Immunology
Daniela Bosisio, Roberto Ronca, Valentina Salvi, Marco Presta, Silvano Sozzani
Lymph node (LN) expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Human dendritic cells (DCs), subdivided into two main subsets, namely conventional DCs (cDCs) and plasmacytoid DCs (pDCs), are professional antigen presenting cells endowed with the capability to produce soluble mediators regulating inflammation and tissue repair. cDCs support angiogenesis in secondary LNs both directly and indirectly through the secretion of vascular endothelial growth factor-A (VEGF)-A and VEGF-C and the production of several other mediators endowed with angiogenic properties...
June 4, 2018: Current Opinion in Immunology
Kathy D McCoy, Aline Ignacio, Markus B Geuking
The trillions of microbes that colonize mucosal surfaces are critical for educating the immune system and microbial-derived signals continually shape and set the tone of immune responses. Although Type 2 immune responses are important for mediating protection from helminth infection they also underlie atopy and allergy. Microbes modulate Type 2 immune responses through effects on Type 2 cytokines, dendritic cells and regulatory T cells. Microbial colonization in the gut, the lung and the skin during an early and critical time period in immune development appears to be of particular importance for tolerance induction and regulation of aberrant Type 2 immune responses...
June 1, 2018: Current Opinion in Immunology
Madelene W Dahlgren, Ari B Molofsky
Group 2 innate lymphoid cells (ILC2) are a subset of innate lymphocytes that responds to local, tissue-derived signals and initiates allergic immune responses. ILC2 activation promotes the recruitment of eosinophils, polarization of alternatively activated macrophages, and tissue-remodeling, processes associated with the 'weep and sweep' response to helminthic worm colonization and infection. ILC2s also coordinate both physiologic and pathologic type 2 allergic immune responses, including promoting normal tissue development and remodeling and driving allergic pathology such as atopic dermatitis and allergic asthma...
May 31, 2018: Current Opinion in Immunology
Marc Permanyer, Berislav Bošnjak, Reinhold Förster
Immune cells continuously recirculate through lymph vessels en route from peripheral tissues to the blood. Leuyte trafficking into and within lymph vessels is mediated by an interply with lymphatic endothelial cells (LECs). However, lymphatic vessels are much more than mere conduits for fluid and immune cell transport. Data accumulating during past several years indicate that LECs support T cell survival, induce tolerance to self-antigens, inhibit exaggerated T cell proliferation during immune response and maintain T cell memory...
May 29, 2018: Current Opinion in Immunology
Jayden Logan, Severine Navarro, Alex Loukas, Paul Giacomin
Infection with helminths has been associated with lower rates of asthma and other allergic diseases. This has been attributed, in part, to the ability of helminths to induce regulatory T cells that suppress inappropriate immune responses to allergens. Recent compelling evidence suggests that helminths may promote regulatory T cell expansion or effector functions through either direct (secretion of excretory/secretory molecules) or indirect mechanisms (regulation of the microbiome). This review will discuss key findings from human immunoepidemiological observations, studies using animal models of disease, and clinical trials with live worm infections, discussing the therapeutic potential for worms and their secreted products for treating allergic inflammation...
May 28, 2018: Current Opinion in Immunology
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