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Pei-Hui Wang, Sin-Yee Fung, Wei-Wei Gao, Jian-Jun Deng, Yun Cheng, Vidyanath Chaudhary, Kit-San Yuen, Ting-Hin Ho, Ching-Ping Chan, Yan Zhang, Kin-Hang Kok, Wanling Yang, Chi-Ping Chan, Dong-Yan Jin
STING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2'3'-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production...
March 14, 2018: Nucleic Acids Research
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
March 1, 2018: Cancer Treatment Reviews
Timothy J Green, Peter Speck
The Pacific oyster, Crassostrea gigas , is becoming a valuable model for investigating antiviral defense in the Lophotrochozoa superphylum. In the past five years, improvements to laboratory-based experimental infection protocols using Ostreid herpesvirus I (OsHV-1) from naturally infected C. gigas combined with next-generation sequencing techniques has revealed that oysters have a complex antiviral response involving the activation of all major innate immune pathways. Experimental evidence indicates C. gigas utilizes an interferon-like response to limit OsHV-1 replication and spread...
March 16, 2018: Viruses
Sara Montserrat-Sangrà, Laura Ordeix, Pamela Martínez-Orellana, Laia Solano-Gallego
Canine leishmaniosis has a wide range of disease severity from mild (stage I), to severe (stages II-III), or very severe disease (stage IV). The objective of the study was to evaluate and compare serum antibody levels, Leishmania infantum specific IFN-γ production and TLR2 and TLR4 transcripts in non-stimulated blood from dogs with different clinical stages at the time of diagnosis as well as blood parasitemia. Enzyme-Linked ImmunoSorbent Assay (ELISAs) were performed to determine serum antibody levels and IFN-γ production and quantitative polymerase chain reaction ( q PCRs) in order to determine blood parasite load and TLR2 and TLR4 transcripts...
March 16, 2018: Veterinary Sciences
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Tatsuo Kanda, Shin Yasui, Masato Nakamura, Shingo Nakamoto, Koji Takahashi, Shuang Wu, Reina Sasaki, Yuki Haga, Sadahisa Ogasawara, Tomoko Saito, Kazufumi Kobayashi, Soichiro Kiyono, Yoshihiko Ooka, Eiichiro Suzuki, Tetsuhiro Chiba, Hitoshi Maruyama, Fumio Imazeki, Mitsuhiko Moriyama, Naoya Kato
Background: Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. Results: All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR...
February 20, 2018: Oncotarget
Peng You, Ning Chen, Lin Su, Tao Peng, Guodong Chen, Yulan Liu
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
April 2018: Experimental and Therapeutic Medicine
Di Wang, Qian Li, Yidi Qu, Mengya Wang, Lanzhou Li, Yang Liu, Yu Li
Gloeostereum incarnatum , a precious edible mushroom, displays anti-bacterial and anti-inflammatory activities; however, its immunomodulatory effect has not been studied yet. The present study aimed to investigate whether polysaccharide compositions of G. incarnatum polysaccharides (GIPS) possess immunomodulatory and immuno-enhancing effects in a Cyclophosphamide monohydrate (CTX)-induced BALB/c mice model. The 28-day GIPS administration at doses of 0.1, 0.3 and 0.9 g/kg remarkably reversed the bodyweight loss, increased the thymic index and promoted T lymphocyte proliferation in CTX-induced immunosuppressed mice...
April 2018: Experimental and Therapeutic Medicine
Peijuan Wang, Yan Lu, Si Chen, Yue Chen, Chunping Hu, Yawei Zuo
Autoimmune abnormality is one of the main causes of premature ovarian failure (POF). Bu Shen Huo Xue formula (BSHXF), a traditional Chinese medicine formula, has been clinically used for the treatment of patients with POF in China. Regulatory T cells (Tregs) are important in the pathogenesis of autoimmune POF. The aim of the present study was to evaluate the immunoprotective effects of BSHXF on POF and the underlying mechanisms. An experimental autoimmune POF model was induced in B6AF1 mice with zona pellucida 3 (ZP3) fragments...
April 2018: Experimental and Therapeutic Medicine
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
Jiwoon Jeong, Seeun Kim, Changhoon Park, Ikjae Kang, Kee Hwan Park, Hee Jin Ham, Chanhee Chae
The objective of this field study was to evaluate the reproductive performance of sows after vaccination with a porcine reproductive and respiratory syndrome (PRRS) subunit vaccine (PRRSFREE PRRS subunit vaccine, Reber Genetics, Taiwan, Republic of China) under field conditions. The study was performed in three farms with endemic infections with both PRRS virus (PRRSV)-1 and PRRSV-2, a situation representative of most Korean farms. Pregnant sows were immunised intramuscularly with 2.0 ml of the PRRS subunit vaccine at 58 and 79 days of gestation (eight and five weeks antepartum) according to the manufacturer's recommendation...
March 15, 2018: Veterinary Record
Luis Malpica, Agustin Pimentel, Isildinha M Reis, Eduardo Gotuzzo, Lazaros Lekakis, Krishna Komanduri, Thomas Harrington, Glen N Barber, Juan C Ramos
Adult T-cell leukemia/lymphoma (ATLL) is a fatal disease caused by human T-cell leukemia virus type 1 (HTLV-1). We retrospectively analyzed 195 patients with ATLL (lymphomatous n = 96, acute n = 80, unfavorable chronic n = 7, chronic n = 5, smoldering n = 3, and unclassified n = 4) diagnosed between 1987 and 2016 (median age 52 years, 77% Afro-Caribbean). Hypercalcemia was associated with acute ATLL (65%, vs 23% lymphomatous) ( P = .012). The median survival for patients treated with modern therapies between 2000 and 2016 was 4...
March 27, 2018: Blood Advances
Liping Qian, Yibo Zuo, Wenjun Deng, Ying Miao, Jin Liu, Yukang Yuan, Tingting Guo, Liting Zhang, Jun Jin, Jun Wang, Hui Zheng
Type-I interferons (IFN-I) are widely used for antiviral immunotherapy in clinic. Therefore, identification of the regulators of IFN-I antiviral activity is important for developing novel targets for IFN-based antiviral therapy. Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) is critical for cellular inflammatory responses. However, the roles of MCPIP1 in interferons (IFNs)-mediated antiviral immunity are unexplored. In this study, we demonstrate for the first time that MCPIP1 is an important positive regulator of IFNs antiviral activity...
March 12, 2018: Biochemical and Biophysical Research Communications
Jeong-Eun Kwon, Seon-Yeong Lee, Hyeon-Beom Seo, Young-Mee Moon, Jun-Geol Ryu, Kyung-Ah Jung, Joo-Yeon Jhun, Jin-Sil Park, Soo-Seok Hwang, Joo-Myeong Kim, Gap Ryol Lee, Sung-Hwan Park, Mi-La Cho
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that functions in cooperation with various cofactors to regulate gene expression. In the immune system, YY1 enhances cytokine production and T helper (Th) 2 effector cell differentiation, resulting in the activation of inflammation. However, no studies have reported the role of YY1 in Th17 cell regulation, which is implicated in rheumatoid arthritis (RA). We investigated the expression of YY1 in Th17 cells in vitro and revealed increased levels of YY1 mRNA and protein...
March 12, 2018: Immunology Letters
Richard Lindqvist, Chaitanya Kurhade, Jonathan D Gilthorpe, Anna K Överby
BACKGROUND: Flaviviruses are a group of diverse and emerging arboviruses and an immense global health problem. A number of flaviviruses are neurotropic, causing severe encephalitis and even death. Type I interferons (IFNs) are the first line of defense of the innate immune system against flavivirus infection. IFNs elicit the concerted action of numerous interferon-stimulated genes (ISGs) to restrict both virus infection and replication. Viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible) is an ISG with broad-spectrum antiviral activity against multiple flaviviruses in vitro...
March 15, 2018: Journal of Neuroinflammation
Jarrod S Johnson, Sasha Y Lucas, Lynn M Amon, Stephanie Skelton, Rodolfo Nazitto, Sara Carbonetti, D Noah Sather, Dan R Littman, Alan Aderem
Myeloid dendritic cells (DCs) have the innate capacity to sense pathogens and orchestrate immune responses. However, DCs do not mount efficient immune responses to HIV-1, primarily due to restriction of virus reverse transcription, which prevents accumulation of viral cDNA and limits its detection through the cGAS-STING pathway. By allowing reverse transcription to proceed, we find that DCs detect HIV-1 in distinct phases, before and after virus integration. Blocking integration suppresses, but does not abolish, activation of the transcription factor IRF3, downstream interferon (IFN) responses, and DC maturation...
March 14, 2018: Cell Host & Microbe
Franck Maunoury, Aurore Clément, Chizoba Nwankwo, Laurie Levy-Bachelot, Armand Abergel, Vincent Di Martino, Eric Thervet, Isabelle Durand-Zaleski
OBJECTIVE: To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment. DESIGN: This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context...
2018: PloS One
Marco Pio La Manna, Valentina Orlando, Paolo Li Donni, Guido Sireci, Paola Di Carlo, Antonio Cascio, Francesco Dieli, Nadia Caccamo
We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells...
2018: PloS One
Larisa J Geskin, James J Damiano, Christina C Patrone, Lisa H Butterfield, John M Kirkwood, Louis D Falo
In the current era of checkpoint inhibitors, some patients with metastatic melanoma have shown a significant improvement in survival. However, optimization of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) vaccines have been shown in clinical trials to be safe and capable of inducing tumor-specific immunity as well as occasional objective clinical responses. Here, we conducted a three-arm pilot clinical study in 15 patients with metastatic melanoma to evaluate three types of MODC vaccines, differing only by strategies of tumor antigen delivery...
March 14, 2018: Melanoma Research
Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
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