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Trends in Immunology

Ivan Budnik, Alexander Brill
Deep vein thrombosis (DVT) is a major origin of morbidity and mortality. While DVT has long been considered as blood coagulation disorder, several recent lines of evidence demonstrate that immune cells and inflammatory processes are involved in DVT initiation. Here, we discuss these mechanisms, in particular, the role of immune cells in endothelial activation, and the immune cascades leading to expression of adhesion receptors on endothelial cells. We analyze the specific recruitment and functional roles of different immune cells, such as mast cells and leukocytes, in DVT...
May 15, 2018: Trends in Immunology
Julie Y Zhou, Douglas M Oswald, Kelsey D Oliva, Lori S C Kreisman, Brian A Cobb
Carbohydrates, or glycans, are as integral to biology as nucleic acids and proteins. In immunology, glycans are well known to drive diverse functions ranging from glycosaminoglycan-mediated chemokine presentation and selectin-dependent leukocyte trafficking to the discrimination of self and non-self through the recognition of sialic acids by Siglec (sialic acid-binding Ig-like lectin) receptors. In recent years, a number of key immunological discoveries are driving a renewed and burgeoning appreciation for the importance of glycans...
May 11, 2018: Trends in Immunology
Chung-Han Lee, Roman Yelensky, Karin Jooss, Timothy A Chan
Antitumor rejection by the immune system is a complex process that is regulated by several factors. Among these factors are the quality and quantity of mutational events that occur in cancer cells. Perhaps one of the most important types of mutations that influence antitumor immunity is the neoantigen, that is, a non-self-antigen that arises as a result of somatic mutation. Recent work has demonstrated that neoantigens hold significant promise for developing new diagnostic and therapeutic modalities. Therapeutic targeting of neoantigens is important for achieving benefit following therapy with immune checkpoint blockade agents or for cancer vaccines targeting mutations...
May 8, 2018: Trends in Immunology
Nick Huang, Andras Perl
Metabolic pathways are now well recognized as important regulators of immune differentiation and activation, and thus influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanistic target of rapamycin (mTOR) has emerged as a key sensor of metabolic stress and an important mediator of proinflammatory lineage specification. Metabolic pathways control the production of mitochondrial reactive oxygen species (ROS), which promote mTOR activation and also modulate the antigenicity of proteins, lipids, and DNA, thus placing ROS at the heart of metabolic disturbances during pathogenesis of SLE...
May 5, 2018: Trends in Immunology
Juan Rivera-Correa, Ana Rodriguez
Antiself antibodies are most commonly associated with autoimmune disorders, but a large body of evidence indicates that they are also present in numerous infectious diseases. These autoimmune antibodies appear transiently during infection with a number of viruses, bacteria, and parasites and in some cases have been associated with the development of autoimmune disorders that develop after infection has been cleared. Traditionally these infection-associated autoantibodies are considered an erroneous byproduct of a legitimate immune response, but their possible role in the clearance of microbes and infected cells or inhibition of host-cell invasion suggests that they may be present because of their beneficial protective role against various infections...
April 30, 2018: Trends in Immunology
Joannie M Allaire, Shauna M Crowley, Hong T Law, Sun-Young Chang, Hyun-Jeong Ko, Bruce A Vallance
The gastrointestinal (GI) tract represents a unique challenge to the mammalian immune system. It must tolerate the presence of the luminal microbiota and thus not respond to their products, but still protect the intestinal mucosa from potentially harmful dietary antigens and invading pathogens. The intestinal epithelium, composed of a single layer of cells, is crucial for preserving gut homeostasis and acts both as a physical barrier and as a coordinating hub for immune defense and crosstalk between bacteria and immune cells...
April 28, 2018: Trends in Immunology
Michael Bauer, Sebastian Weis, Mihai G Netea, Reinhard Wetzker
Recent investigations reveal memory-like adaptive responses of the innate immune system to sequential pathogen challenge. Of note, opposing effects that include both sensitization ('training') and desensitization ('tolerance') have been reported. While hitherto the nature of the pathogen was thought to be of prime importance, we propose that pathogen dose plays a key role in determining these opposing effects. Within this concept, training and tolerance of innate immune cells emerge as adaptive responses to increasing pathogen load...
April 28, 2018: Trends in Immunology
Martin S Davey, Carrie R Willcox, Alfie T Baker, Stuart Hunter, Benjamin E Willcox
γδ T cells are unconventional lymphocytes commonly described as 'innate-like' in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges...
April 18, 2018: Trends in Immunology
Claire Vanpouille-Box, Silvia C Formenti
Tumors that elude infiltration by CD8+ T lymphocytes are particularly resistant to multiple forms of treatment, including immune checkpoint blockade. Stromal transforming growth factor (TGF)-β appears to play a key role in this process, potentially constituting a target for novel combinatorial regimens tackling immune-excluded neoplasms.
March 26, 2018: Trends in Immunology
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No abstract text is available yet for this article.
March 21, 2018: Trends in Immunology
Rachel Golub, Jonathan Tan, Takeshi Watanabe, Andrea Brendolan
The mammalian spleen is a peripheral lymphoid organ that plays a central role in host defense. Consequently, the lack of spleen is often associated with immunodeficiency and increased risk of overwhelming infections. Growing evidence suggests that non-hematopoietic stromal cells are central players in spleen development, organization, and immune functions. In addition to its immunological role, the spleen also provides a site for extramedullary hematopoiesis (EMH) in response to injuries. A deeper understanding of the biology of stromal cells is therefore essential to fully comprehend how these cells modulate the immune system during normal and pathological conditions...
March 19, 2018: Trends in Immunology
Melanie R Shakespear, Abishek Iyer, Catherine Youting Cheng, Kaustav Das Gupta, Amit Singhal, David P Fairlie, Matthew J Sweet
Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes...
March 19, 2018: Trends in Immunology
Tomasz P Wypych, Benjamin J Marsland
The human body and its resident microbiota form a complex ecosystem, shaped by both inherited and environmental factors. The use of antibiotics represents an extreme example of environmental pressure and can broadly disrupt the microbial landscape. The benefits that antibiotics have brought to modern medicine are unquestionable; however, their overuse comes with consequences, including the potential for secondary infections by opportunistic pathogens and the spread of antibiotic resistance. Here, we discuss the implications of microbial dysbiosis driven by antibiotics, with a focus on potential links with allergy and asthma...
March 14, 2018: Trends in Immunology
Jordan Z Zhou, Sing Sing Way, Kang Chen
No abstract text is available yet for this article.
April 2018: Trends in Immunology
Aurélie Poli, Tatiana Michel, Neha Patil, Jacques Zimmer
Immune responses are critical for the maintenance of homeostasis but can also upset the equilibrium, depending on the context and magnitude of the response. Natural killer (NK) cells are well known for their important roles in antiviral and antitumor immune responses, and they are currently used, mostly under optimized forms, as immunotherapeutic agents against cancer. Nevertheless, with accumulating examples of deleterious effects of NK cells, it is paramount to consider their negative contributions. Here, we critically review and comment on the literature surrounding undesirable aspects of NK cell activity, focusing on situations where they play a harmful rather than a protective role...
February 26, 2018: Trends in Immunology
Ashley Lau, Lori West, Stefan G Tullius
Transplantation outcomes are known to be affected by multiple factors, including donor and recipient sex. Aside from the physiological characteristics of male and female donor allografts, accumulating evidence suggests that additional features underlie sex-specific immune responses that affect graft survival. We discuss here aspects of innate and adaptive alloimmunity that are specific to males and females in the context of underlying genetic and hormonal factors. These differences likely contribute to the observed disparities in graft survival...
May 2018: Trends in Immunology
Martijn H den Brok, Tonke K Raaijmakers, Estel Collado-Camps, Gosse J Adema
Lipid droplets (LDs) were initially described as fat storage organelles in adipocytes, but are increasingly recognized as dynamic players in lipid metabolism, with important roles not only in diseases such as diabetes and cancer, but also in immune regulation. Alterations in immune cell function, such as myeloid cell activation, are connected to profound changes in LD numbers and LD protein composition. Thus, these organelles appear to be essential to metabolically support immune responses, and have a vital role in antigen crosspresentation, interferon (IFN) responses, production of inflammatory mediators, and pathogen clearance...
May 2018: Trends in Immunology
Giorgio Trinchieri
In addition to exogenous ligands derived from pathogens, natural killer (NK) and other innate cells can recognize endogenous ligands that often act as markers of stress or damage. A recent study reports that one of these receptors, human NKp44, recognizes PDGF-DD, providing a rare example of the recognition of a soluble growth factor as a stress signal. The recognition of PDGF-DD induces the secretion of cytokines with antitumor activity.
May 2018: Trends in Immunology
Tao Gong, Yanqing Yang, Tengchuan Jin, Wei Jiang, Rongbin Zhou
The assembly of the NLRP3 inflammasome can promote the release of IL-1β/IL-18 and initiate pyroptosis. Accordingly, the dysregulation of NLRP3 inflammasome activation is involved in a variety of human diseases, including gout, diabetes, and Alzheimer's disease. NLRP3 can sense a variety of structurally unrelated pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to trigger inflammation, but the unifying mechanism of NLRP3 activation is still poorly understood. Increasing evidence suggests that intracellular ions, such as K+ , Ca2+ , and Cl- , have a significant role in NLRP3 inflammasome activation...
May 2018: Trends in Immunology
Mangalakumari Jeyanathan, Yushi Yao, Sam Afkhami, Fiona Smaill, Zhou Xing
Despite some major progress made in developing tuberculosis (TB) vaccine strategies, with a dozen novel vaccines currently in the clinical pipeline, the world is still missing an effective TB vaccine. This questions whether any major breakthroughs can be achieved without making a drastic departure from the current strategy, which creates a state of 'near-natural immunity', imitating the natural immunity developed after Mycobacterium tuberculosis (Mtb) infection. Here, we argue instead that mounting evidence suggests an effective strategy ought to induce a state of all-around 'un-natural' immunity comprising trained innate immunity (TII), tissue-resident memory T cells (TRM ), and anti-Mtb surface antibodies in the lung...
May 2018: Trends in Immunology
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