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Immunological pathways

Neha M Sahasrabudhe, Martin Beukema, Lingmin Tian, Berit Troost, Jan Scholte, Erik Bruininx, Geert Bruggeman, Marco van den Berg, Anton Scheurink, Henk A Schols, Marijke M Faas, Paul de Vos
Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered...
2018: Frontiers in Immunology
Holger Winkels, Erik Ehinger, Melanie Vassallo, Konrad Buscher, Huy Dinh, Kouji Kobiyama, Anouk Hamers, Clément Cochain, Ehsan Vafadarnejad, Antoine-Emmanuel Saliba, Alma Zernecke, Akula Pramod, Amlan Ghosh, Nathaly Anto Michel, Natalie Hoppe, Ingo Hilgendorf, Andreas Zirlik, Catherine Hedrick, Klaus Ley, Dennis Wolf
<u>Rationale:</u> Atherosclerosis is a chronic inflammatory disease that is driven by the interplay of pro- and anti-inflammatory leukocytes in the aorta. Yet, the phenotypic and transcriptional diversity of aortic leukocytes is only poorly understood. <u>Objective:</u> We characterized leukocytes from healthy and atherosclerotic mouse aortas in-depth by single cell RNA-sequencing (scRNAseq) and mass cytometry (CyTOF) to define an atlas of the immune cell landscape in atherosclerosis...
March 15, 2018: Circulation Research
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Nan Shwe Nwe Htun, Peter Odermatt, Ivan Müller, Peiling Yap, Peter Steinmann, Christian Schindler, Markus Gerber, Rosa Du Randt, Cheryl Walter, Uwe Pühse, Jürg Utzinger, Nicole Probst-Hensch
BACKGROUND: Low- and middle-income countries are facing a dual disease burden with infectious diseases (e.g., gastrointestinal tract infections) and non-communicable diseases (e.g., diabetes) being common. For instance, chronic parasite infections lead to altered immune regulatory networks, anemia, malnutrition, and diarrhea with an associated shift in the gut microbiome. These can all be pathways of potential relevance for insulin resistance and diabetes. The aim of this study was to investigate the association between common gastrointestinal tract infections and glycemia in children from non-fee paying schools in South Africa...
March 15, 2018: PLoS Neglected Tropical Diseases
Zhe Du, Shujun Wang, Bing Yue, Ying Wang, You Wang
T-cells, second only to macrophages, are often considered as the potential cells involved in debris-related failure of arthroplasty. Here, we assessed the effects of particulate wear debris on T-cells and inflammatory reactions. Blood samples from 25 donors were incubated with polyether-ether-ketone (PEEK) and cobalt-chromium-molybdenum (CoCrMo) particles generated by custom cryo-milling and pulverization. The T-cell phenotypes were assessed using immunostaining and flow cytometry. For the in vivo study, 0...
February 16, 2018: Oncotarget
Paramita Saha, Kasturi Datta
Cancer is a complex, multi-factorial, multi-stage disease and a global threat to human health. Early detection of nature and stage of cancer is highly crucial for disease management. Recent studies have proved beyond any doubt about the involvement of the ubiquitous, myriad ligand binding, multi-functional human protein, hyaluronan-binding protein 1 (HABP1), which is identical to the splicing factor associated protein (p32) and the receptor of the globular head of the complement component (gC1qR) in tumorigenesis and cancer metastasis...
February 13, 2018: Oncotarget
Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan
Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches...
2018: Frontiers in Immunology
Zhilin Zeng, Miao Li, Jinkun Chen, Qinghai Li, Qin Ning, Jianping Zhao, Yongjian Xu, Jungang Xie, Jun Yu
Background: Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease characterized by inflammatory cells activation and production of inflammatory mediators. Methyl-CpG-binding domain protein 2 (MBD2) plays an important role in diverse immunological disorders by regulating immune cell functions, such as differentiation and mediator secretion. However, the role of MBD2 in COPD remains unknown. Methods: MBD2 protein expression in lung tissues of patients with COPD and cigarette smoke (CS)-exposed mice were evaluated by Western blot and immunohistochemistry...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
F Andrea Sass, Michael Fuchs, Matthias Pumberger, Sven Geissler, Georg N Duda, Carsten Perka, Katharina Schmidt-Bleek
Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary...
March 13, 2018: International Journal of Molecular Sciences
Michael Schörghuber, Sonja Fruhwald
Nutritional management is a cornerstone of therapy for patients who are critically ill. Data show that enteral nutrition is better than parenteral nutrition with regard to the morbidity of critcally ill patients, especially for infectious complications. These findings suggest that feeding patients enterally has other beneficial effects besides delivering nutrients. In the absence of enteral nutrition, the mucosal architecture changes distinctly, leading to an impairment in function of the gastrointestinal barrier...
April 2018: Lancet. Gastroenterology & Hepatology
Jee Youn Hwang, Kesavan Markkandan, Mun Gyeong Kwon, Jung Soo Seo, Seung-Il Yoo, Seong Don Hwang, Maeng-Hyun Son, Junhyung Park
Olive flounder (Paralichthys olivaceus) is one of the most valuable marine aquatic species in South Korea and faces tremendous exposure to the viral hemorrhagic septicemia virus (VHSV). Given the growing importance of flounder, it is therefore essential to understand the host defense of P. olivaceus against VHSV infection, but studies on its immune mechanism are hindered by the lack of genomic resources. In this study, the P. olivaceus was infected with disease-causing VHSV isolates, ADC-VHS2012-11 and ADC-VHS2014-5 which showed moderate virulent (20% mortality) and high virulent (65% mortality), in order to investigate the effect of difference in pathogenicity in head kidney during 1, 3, 7 days of post-infection using Illumina sequencing...
March 9, 2018: Fish & Shellfish Immunology
Julian A Gingold, Dandan Zhu, Dung-Fang Lee, Ahmed Kaseb, Jian Chen
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the two most common primary liver cancers, represent the second most common cancer-related cause of death worldwide, with most cases being diagnosed at an advanced stage. Recent genome-wide studies have helped to elucidate the molecular pathogenesis and genetic heterogeneity of liver cancers. This review of the genetic landscape of HCC and iCCA discusses the most recent findings from genomic profiling and the current understanding of the pathways involved in the initiation and progression of liver cancer...
March 9, 2018: Trends in Molecular Medicine
Masakatsu Yamashita, Makoto Kuwahara
Although Bach2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) plays an important role in regulating Th2 cell differentiation and type-2 immune responses, the underlying molecular mechanisms remain unclear. Our current studies demonstrate that Bach2 associates with Batf (basic leucine zipper transcription factor ATF-like) family transcription factors and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the interferon regulatory factor 4 (Irf4)-containing Batf complex to activator protein 1 (AP-1) motifs in the Th2 cytokine gene locus and suppresses Th2 cytokine production and/or Th2 cell differentiation...
February 24, 2018: International Immunology
V Venturi, T Masek, M Pospisek
Elevated levels of eukaryotic initiation factor 4E (eIF4E) are implicated in neoplasia, with cumulative evidence pointing to its role in the etiopathogenesis of hematological diseases. As a node of convergence for several oncogenic signaling pathways, eIF4E has attracted a great deal of interest from biologists and clinicians whose efforts have been targeting this translation factor and its biological circuits in the battle against leukemia. The role of eIF4E in myeloid leukemia has been ascertained and drugs targeting its functions have found their place in clinical trials...
March 12, 2018: Physiological Research
Simon P Keam, Twishi Gulati, Cristina Gamell, Franco Caramia, Cheng Huang, Ralf B Schittenhelm, Oded Kleifeld, Paul J Neeson, Ygal Haupt, Scott G Williams
INTRODUCTION: The development of radioresistance in prostate cancer (PCa) is an important clinical issue and is still largely uninformed by personalized molecular characteristics. The aim of this study was to establish a platform that describes the early oncoproteomic response of human prostate tissue to radiation therapy (RT) using a prospective human tissue cohort. METHODS: Fresh and fixed transperineal biopsies from eight men with clinically localized tumors were taken prior to and 14 days following a single fraction of high-dose-rate brachytherapy...
March 9, 2018: Prostate
Ciana Diskin, Eva M Pålsson-McDermott
Traditionally cellular respiration or metabolism has been viewed as catabolic and anabolic pathways generating energy and biosynthetic precursors required for growth and general cellular maintenance. However, growing literature provides evidence of a much broader role for metabolic reactions and processes in controlling immunological effector functions. Much of this research into immunometabolism has focused on macrophages, cells that are central in pro- as well as anti-inflammatory responses-responses that in turn are a direct result of metabolic reprogramming...
2018: Frontiers in Immunology
Ketan K Marballi, Amelia L Gallitano
While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly...
2018: Frontiers in Behavioral Neuroscience
Joana Maia, Sergio Caja, Maria Carolina Strano Moraes, Nuno Couto, Bruno Costa-Silva
Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios...
2018: Frontiers in Cell and Developmental Biology
Hatem Soliman, Fatema Khambati, Hyo S Han, Roohi Ismail-Khan, Marilyn M Bui, Daniel M Sullivan, Scott Antonia
Background: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. Materials and Methods: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks...
February 9, 2018: Oncotarget
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