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Guanhua Song, Bingyu Liu, Zhihui Li, Haifeng Wu, Peng Wang, Kai Zhao, Guosheng Jiang, Lei Zhang, Chengjiang Gao
TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo...
October 24, 2016: Nature Immunology
Jürgen Maibaum, Sha-Mei Liao, Anna Vulpetti, Nils Ostermann, Stefan Randl, Simon Rüdisser, Edwige Lorthiois, Paul Erbel, Bernd Kinzel, Fabrice A Kolb, Samuel Barbieri, Julia Wagner, Corinne Durand, Kamal Fettis, Solene Dussauge, Nicola Hughes, Omar Delgado, Ulrich Hommel, Ty Gould, Aengus Mac Sweeney, Bernd Gerhartz, Frederic Cumin, Stefanie Flohr, Anna Schubart, Bruce Jaffee, Richard Harrison, Antonio Maria Risitano, Jörg Eder, Karen Anderson
Complement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways. The protease factor D (FD) is essential for this amplification process, which, when dysregulated, predisposes individuals to diverse disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinuria (PNH)...
October 24, 2016: Nature Chemical Biology
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Magdalena Paolino, Josef M Penninger
The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases...
October 21, 2016: Cancers
Manickam Sugumaran, Hanine Barek
Animals synthesize melanin pigments for the coloration of their skin and use it for their protection from harmful solar radiation. Insects use melanins even more ingeniously than mammals and employ them for exoskeletal pigmentation, cuticular hardening, wound healing and innate immune responses. In this review, we discuss the biochemistry of melanogenesis process occurring in higher animals and insects. A special attention is given to number of aspects that are not previously brought to light: (1) the molecular mechanism of dopachrome conversion that leads to the production of two different dihydroxyindoles; (2) the role of catecholamine derivatives other than dopa in melanin production in animals; (3) the critical parts played by various biosynthetic enzymes associated with insect melanogenesis; and (4) the presence of a number of important gaps in both melanogenic and sclerotinogenic pathways...
October 20, 2016: International Journal of Molecular Sciences
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Handan Tan, Bolin Deng, Hongsong Yu, Yi Yang, Lin Ding, Qi Zhang, Jieying Qin, Aize Kijlstra, Rui Chen, Peizeng Yang
Interleukin-1 (IL-1) and the IL-1 receptor (IL-1R) family play an important role in the pathogenesis of inflammatory diseases. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of IL-1 and IL-1R family genes with Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD) in Han Chinese. The case-control study was divided into two stages and included 419 VKH cases, 1063 BD cases and 1872 healthy controls. The MassARRAY platform (Sequenom), iPLEX Gold Assay and TaqMan SNP assays were used to score genotypes of 24 SNPs...
October 24, 2016: Scientific Reports
Thiago Aparecido da Silva, Maria Cristina Roque-Barreira, Arturo Casadevall, Fausto Almeida
Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated...
October 24, 2016: Scientific Reports
Xuyang Zheng, Chuantao Ye, Jieru Zhao, Peiyu Bian, Ying Zhang, Zhansheng Jia
Objective To observe the alterations of innate immunity related long non-coding RNAs (lncRNAs) in exosomes extracted from the plasma of hemorrhagic fever with renal syndrome (HFRS) patients, and analyze their relationship with the disease stage and severity. Methods Exosomes were extracted from the plasma samples of HFRS patients, healthy controls and recovered HFRS patients. Transmission electronic microscopy and Western blotting were performed to confirm the efficiency of the extraction. lncRNA profiles in the different groups were determined by high-throughput sequencing...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Lijun Sun, Jingying Sun, Xueping Huo, Yaping Li, Yuan Li, Xin Xie, Jun Hu
Objective To explore the effect of Toll-like receptor 4 (TLR4) activation on melanogenesis in melanocytes. Methods The primary melanocytes were isolated, cultured and then stimulated by TLR4 agonist lipopolysaccharide (LPS). Firstly, the melanin content changes were detected in melanocytes, and then quantitative real-time PCR and Western blotting were employed to determine the expression levels of pre-melanosomal protein (Pmel17), tyrosinase (TYR) and microphthalmia-associated transcription factor (MITF). Finally, the melanosomes were observed by electron microscopy...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Nicole Y K Li-Jessen, Michael Powell, Ae-Jin Choi, Byung-Joo Lee, Susan L Thibeault
OBJECTIVES/HYPOTHESIS: High-mobility group box 1 (HMGB1) is a chromatin-binding protein located in the cell nucleus. Following injury, immunocompetent cells secrete HMGB1 to the extracellular milieu under the stimulation of proinflammatory cytokines. Extracellular HMGB1 acts a danger signal that instigates the innate immunity and tissue repair. We previously reported HMGB1 in the vocal fold extracellular compartment between day 3 and day 7 following surgical injury. In this study, we further investigated the cell source of HMGB1 and the relationship of proinflammatory cytokine expression and HMGB1 translocation in wounded vocal folds...
October 24, 2016: Laryngoscope
R F Godino, A I Fernández
Mx1 (Myxovirus (Influenza virus) resistance 1, interferon-inducible protein p78) gene has been implicated in the resistance to a wide range of RNA viruses including influenza A in several species such as Sus scrofa. In the present study a 28-bp deletion in exon 14 of the Mx1 gene has been identified in Iberian domestic pigs but not in other domestic breeds neither in wild boars. The mutation produces a frameshift giving a protein with 6 amino acid substitutions and the extension of the C-terminal region with additional 20 amino acids with respect to the wild type MX1 protein...
September 2016: Postdoc Journal: a Journal of Postdoctoral Research and Postdoctoral Affairs
Silvia Pesce, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro
Innate and adaptive immunity has evolved complex molecular mechanisms regulating immune cell migration to facilitate the dynamic cellular interactions required for its function involving the chemokines and their receptors. One important chemokine receptor in the immune system is represented by CCR7. Together with its ligands CCL19 and CCL21, this chemokine receptor controls different arrays of migratory events, both in innate and adaptive immunity, including homing of CD56(bright) NK cells, T cells, and DCs to lymphoid compartments, where T cell priming occurs...
2016: Frontiers in Immunology
Aranzazu Cruz-Adalia, Esteban Veiga
During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases...
2016: Frontiers in Immunology
Juanjuan Zhao, Chao Chen, Mengmeng Guo, Yijin Tao, PanPan Cui, Ya Zhou, Nalin Qin, Jing Zheng, Jidong Zhang, Lin Xu
Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice...
2016: Frontiers in Immunology
Glenn S Tillotson
Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward...
2016: Infectious Diseases
Hadiseh Dadras, Mohammad Reza Hayatbakhsh, William L Shelton, Amin Golpour
The aim of this study was to investigate effects of two dietary medicinal herbs, Rose hip (Rosa canina) and Safflower (Carthamus tinctorius) supplementation on growth performance, haematological, biochemical parameters and innate immune response of in juvenile beluga, Huso huso. Fish (26.3 ± 0.4 g) were allocated into 15 tanks (20 fish per tank) and triplicate groups were fed a control diet or diets containing 1% and 2% of medicinal herbs, respectively. Feed conversion ratio (FCR), specific growth rate (SGR) and condition factor (CF) did not show significant differences (P > 0...
October 20, 2016: Fish & Shellfish Immunology
Julia Fischer, Tabitha Price
Two core questions in the study of speech evolution are whether nonhuman primate signals should be conceived as referential, and what the role of social cognition is in primate communication. Current evidence suggests that the structure of primate vocalizations is largely innate and related to the affective/motivational state of the caller, with a probabilistic and underdetermined relationship between specific events and calls. Moreover, nonhuman primates do not appear to express or comprehend communicative or informative intent, which is in line with a lack of mental state attribution to others...
October 20, 2016: Neuroscience and Biobehavioral Reviews
Huijie Zhang, Xiao-Dong Gao
Synthetic oligodeoxynucleotides containing immunostimulatory CpG motif mimic bacterial DNA and are potent activator of innate and adaptive immune responses. Therefore, CpG ODNs have significant potentials as immunotherapeutic agent for treatment of infectious diseases, allergy and cancer. Many clinical trials involving CpG ODNs either used alone or as adjuvant have been initiated. However, delivery of CpG ODNs to target sites still remains a great challenge due to their extreme susceptibility to nuclease degradation in serum and poor cellular uptake...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Michelle T Graham, Sandra Andorf, Jonathan M Spergel, Talal A Chatila, Kari C Nadeau
PURPOSE OF REVIEW: Food allergies (FAs) are a growing epidemic in western countries with poorly defined etiology. Defined as an adverse immune response to common food allergens, FAs present heterogeneously as a single- or multi-organ response that ranges in severity from localized hives and angioedema to systemic anaphylaxis. RECENT FINDINGS: Current research focusing on epithelial-derived cytokines contends that temporal regulation by these factors impact initial sensitization and persistence of FA responses upon repeated food allergen exposure...
October 2016: Current Allergy and Asthma Reports
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