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Frontiers in Immunology

Masaaki Okamoto, Takahisa Kouwaki, Yoshimi Fukushima, Hiroyuki Oshiumi
RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double-stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of the innate immune responses. The protein comprises N-terminal two caspase activation and recruitment domains (2CARDs), an RNA helicase domain, and the C-terminal domain (CTD). The CTD recognizes 5'-triphosphate viral dsRNA. After recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination essential for RIG-I activation...
2017: Frontiers in Immunology
Stefano Alivernini, Elisa Gremese, Charles McSharry, Barbara Tolusso, Gianfranco Ferraccioli, Iain B McInnes, Mariola Kurowska-Stolarska
MicroRNAs (miRNAs) are small non-coding RNAs that fine-tune the cell response to a changing environment by modulating the cell transcriptome. miR-155 is a multifunctional miRNA enriched in cells of the immune system and is indispensable for the immune response. However, when deregulated, miR-155 contributes to the development of chronic inflammation, autoimmunity, cancer, and fibrosis. Herein, we review the evidence for the pathogenic role of miR-155 in driving aberrant activation of the immune system in rheumatoid arthritis, and its potential as a disease biomarker and therapeutic target...
2017: Frontiers in Immunology
Elina Simanovich, Vera Brod, Maya M Rahat, Michal A Rahat
Tumors survive and progress by evading killing mechanisms of the immune system, and by generating a tumor microenvironment (TME) that reprograms macrophages in situ to produce factors that support tumor growth, angiogenesis, and metastasis. We have previously shown that by blocking the translation of the enzyme inducible nitric oxide synthase (iNOS), miR-146a-5p inhibits nitric oxide (NO) production in a mouse renal carcinoma cell line (RENCA), thereby endowing RENCA cells with resistance to macrophage-induced cell death...
2017: Frontiers in Immunology
Thomas Blank, Tobias Goldmann, Mirja Koch, Lukas Amann, Christian Schön, Michael Bonin, Shengru Pang, Marco Prinz, Michael Burnet, Johanna E Wagner, Martin Biel, Stylianos Michalakis
Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes...
2017: Frontiers in Immunology
Olivia I Coleman, Dirk Haller
The gastrointestinal (GI) tract provides a compartmentalized interface with an enormous repertoire of immune and metabolic activities, where the multicellular structure of the mucosa has acquired mechanisms to sense luminal factors, such as nutrients, microbes, and a variety of host-derived and microbial metabolites. The GI tract is colonized by a complex ecosystem of microorganisms, which have developed a highly coevolved relationship with the host's cellular and immune system. Intestinal epithelial pattern recognition receptors (PRRs) substantially contribute to tissue homeostasis and immune surveillance...
2017: Frontiers in Immunology
Lucía Pastor, Victor Urrea, Jorge Carrillo, Erica Parker, Laura Fuente-Soro, Chenjerai Jairoce, Inacio Mandomando, Denise Naniche, Julià Blanco
During primary HIV infection (PHI), there is a striking cascade response of inflammatory cytokines and many cells of the immune system show altered frequencies and signs of extensive activation. These changes have been shown to have a relevant role in predicting disease progression; however, the challenges of identifying PHI have resulted in a lack of critical information about the dynamics of early pathogenic events. We studied soluble inflammatory biomarkers and changes in T-cell subsets in individuals at PHI (n = 40), chronic HIV infection (CHI, n = 56), and HIV-uninfected (n = 58) recruited at the Manhiça District Hospital in Mozambique...
2017: Frontiers in Immunology
Ioannis Panagoulias, Fotios Karagiannis, Ioanna Aggeletopoulou, Tassos Georgakopoulos, Christos P Argyropoulos, Karolina Akinosoglou, Charalambos Gogos, Athanasios Skoutelis, Athanasia Mouzaki
HIV-1 is transcriptionally active in activated T helper (Th)-cells and inactive in naive or resting memory Th-cells. Ets-2 is a preinduction transcriptional repressor of the IL-2 gene in naive Th-cells and a candidate transcriptional repressor of HIV-1 in the same cells, because the -279 to -250 upstream region of HIV-1-LTR [repressor-activator target sequence (RATS)], that participates in HIV-1-LTR transcriptional silencing, encompasses the AAGGAG Ets-2 binding site. In this proof of concept study, we investigated whether Ets-2 represses the expression of HIV-1...
2017: Frontiers in Immunology
Chengbo Liu, Ze Chen, Wen Li, Lisu Huang, Yongjun Zhang
Bronchopulmonary dysplasia (BPD) is characterized by the premature arrest of alveolar development. Antenatal exposure to inflammation inhibits lung morphogenesis, thereby increasing the risk for the development of BPD. Here, we investigated whether vitamin D (VitD) enhances alveolar development in antenatal lipopolysaccharide (LPS)-treated rats, which is a model for BPD. We used an established animal model of BPD, and random assignment to the control group, LPS group, or LPS with VitD group. Levels of interferon (IFN)-γ and interleukin-4 were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay...
2017: Frontiers in Immunology
Wen-Jing Bai, Chen-Guang Li, Cheng-Cheng Zhang, Li-Hui Xu, Qiong-Zhen Zeng, Bo Hu, Zhou Hong, Xian-Hui He, Dong-Yun Ouyang
CPT-11 is a first-line chemotherapeutic agent for the treatment of colorectal cancer in clinic. Previous studies including ours have demonstrated that CPT-11 is, however, toxic to the intestinal epithelium and resident peritoneal macrophages. By interacting with B1 cells, the resident peritoneal macrophages play critical roles in the maintenance of gastrointestinal homeostasis. It remains therefore elusive whether these peritoneal innate immune cells could be rebuilt spontaneously or artificially after being impaired by CPT-11 administration...
2017: Frontiers in Immunology
Ariel Podhorzer, Melisa Dirchwolf, Andrés Machicote, Santiago Belen, Silvina Montal, Silvia Paz, Hugo Fainboim, Luis G Podestá, Leonardo Fainboim
Killer cell immunoglobulin-like receptor (KIR) genes are known to play a role in the acute phase of hepatitis C virus (HCV) infection. The present study investigated their roles in chronic HCV (CHCV) infection by analyzing the phenotypes and function of natural killer (NK) and T cells that express KIRs. T cells from CHCV patients showed a more differentiated phenotype, and NK cells exhibited an activated profile. These observations are consistent with the increased expression of the degranulation marker CD107a observed after PMA stimulation...
2017: Frontiers in Immunology
Lu Chen, Qian You, Liang Hu, Jian Gao, Qianqian Meng, Wentao Liu, Xuefeng Wu, Qiang Xu
Management of inflammatory bowel disease (IBD) is a real clinical challenge. Despite intense investigation, the mechanisms of IBD remain substantially unidentified. Some inflammatory conditions, such as matrix metalloproteinases (MMPs) and the nuclear factor-κB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathways, are reported to contribute to the development and maintenance of IBD. Regulation of their common upstream signaling, that is, reactive oxygen species (ROS), may be important to control the progression of IBD...
2017: Frontiers in Immunology
Shiyang Li, John W Bostick, Liang Zhou
With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs) represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes- group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin) at the interface of host-environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs...
2017: Frontiers in Immunology
Joe Dan Dunn, Cristina Bosmani, Caroline Barisch, Lyudmil Raykov, Louise H Lefrançois, Elena Cardenal-Muñoz, Ana Teresa López-Jiménez, Thierry Soldati
The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each meal is a potential infection because some bacteria have evolved mechanisms to resist predation. To survive such a hostile environment, D. discoideum has in turn evolved efficient antimicrobial responses that are intertwined with phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery and antimicrobial functions of these pathways are conserved in the mononuclear phagocytes of mammals, which mediate the initial, innate-immune response to infection...
2017: Frontiers in Immunology
Roberta Rovito, Frans H J Claas, Geert W Haasnoot, Dave L Roelen, Aloys C M Kroes, Michael Eikmans, Ann C T M Vossen
Congenital CMV infection (cCMV) is the most common congenital infection causing permanent long-term impairments (LTI). cCMV immunopathogenesis is largely unknown due to the complex interplay between viral, maternal, placental, and child factors. In this study, a large retrospective nationwide cohort of children with cCMV and their mothers was used. HLA-C, HLA-E, and HLA-G were assessed in 96 mother-child pairs in relation to symptoms at birth and LTI at 6 years of age. The mothers were additionally typed for killer cell immunoglobulin-like receptors...
2017: Frontiers in Immunology
Jianyun Liu, Richard M Gallo, Masood A Khan, Gourapura J Renukaradhya, Randy R Brutkiewicz
Neurofibromin 1 (NF1) is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT) cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair) host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways...
2017: Frontiers in Immunology
Massimo Fantini, Justin M David, Olga Saric, Alexander Dubeykovskiy, Yongzhi Cui, Sharon A Mavroukakis, Andrew Bristol, Christina M Annunziata, Kwong Y Tsang, Philip M Arlen
NEO-201 is a novel humanized IgG1 monoclonal antibody that was derived from an immunogenic preparation of tumor-associated antigens from pooled allogeneic colon tumor tissue extracts. It was found to react against a variety of cultured human carcinoma cell lines and was highly reactive against the majority of tumor tissues from many different carcinomas, including colon, pancreatic, stomach, lung, and breast cancers. NEO-201 also exhibited tumor specificity, as the majority of normal tissues were not recognized by this antibody...
2017: Frontiers in Immunology
Anca Dorhoi, Nelita Du Plessis
Heterogeneous populations of myeloid regulatory cells (MRC), including monocytes, macrophages, dendritic cells, and neutrophils, are found in cancer and infectious diseases. The inflammatory environment in solid tumors as well as infectious foci with persistent pathogens promotes the development and recruitment of MRC. These cells help to resolve inflammation and establish host immune homeostasis by restricting T lymphocyte function, inducing regulatory T cells and releasing immune suppressive cytokines and enzyme products...
2017: Frontiers in Immunology
Ivana Z Matić, Branka Kolundžija, Ana Damjanović, Jelena Spasić, Davorin Radosavljević, Marija Đorđić Crnogorac, Nađa Grozdanić, Zorica D Juranić
It was demonstrated that cetuximab-induced tumor regression is based on the effects exerted by immune cells included mainly in the innate immune response. Therefore, the focus of this study was to explore the alterations in the percentages of CD16+, and/or CD56+ lymphocytes, which are comprised of NK cells, and minority of CD56+CD3+ cells, in patients with metastatic colorectal cancer before or 2 months after the treatment with cetuximab-based regimens associated with the response to therapy. The changes in the percentages of lymphocytes and granulocytes in these patients were evaluated as well...
2017: Frontiers in Immunology
Karine Chartrand, Marie-Ève Lebel, Esther Tarrab, Pierre Savard, Denis Leclerc, Alain Lamarre
Although vaccination has been an effective way of preventing infections ever since the eighteenth century, the generation of therapeutic vaccines and immunotherapies is still a work in progress. A number of challenges impede the development of these therapeutic approaches such as safety issues related to the administration of whole pathogens whether attenuated or inactivated. One safe alternative to classical vaccination methods gaining recognition is the use of nanoparticles, whether synthetic or naturally derived...
2017: Frontiers in Immunology
Toshana L Foster, Suzanne Pickering, Stuart J D Neil
Like all viruses, human immunodeficiency viruses (HIVs) and their primate lentivirus relatives must enter cells in order to replicate and, once produced, new virions need to exit to spread to new targets. These processes require the virus to cross the plasma membrane of the cell twice: once via fusion mediated by the envelope glycoprotein to deliver the viral core into the cytosol; and secondly by ESCRT-mediated scission of budding virions during release. This physical barrier thus presents a perfect location for host antiviral restrictions that target enveloped viruses in general...
2017: Frontiers in Immunology
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