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innate response

Suzanne Ostrand-Rosenberg
Myeloid-derived suppressor cells (MDSC) are present in most individuals with cancer where they inhibit adaptive and innate antitumor immunity and are an obstacle to cancer immunotherapies. Chronic inflammation is characteristic of adipose tissue and is a risk factor for the onset and progression of cancer in obese individuals. Because MDSC accumulate in response to inflammation, it has been hypothesized that one of the mechanisms by which obesity promotes malignancy is through the induction of MDSC. This article reviews the data supporting this hypothesis, the role of leptin and fatty acid metabolism in the induction of MDSC, and the surprising finding that although MDSC promote tumor progression, they are protective against some of the metabolic dysfunction associated with obesity...
March 12, 2018: Current Opinion in Immunology
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
Lingling Gan, Xuemei Zhang, Xiuyu Xu, Wenchun Xu, Chang Lu, Jin Cui, Hong Wang
<i>spd1672</i>, a novel <i>Streptococcus pneumoniae</i> (<i>S. pn</i>) gene induced in vivo, has been identified to contribute to the virulence of <i>S. pn</i>; however, the role of <i>spd1672</i> during host innate immune reaction against<i> S. pn</i> infection is unknown. In the present study, mice were infected with wild type D39 and mutant D39Δspd1672 strains. Compared to the D39-infected mice, reduced bacterial load and attenuated inflammatory response were observed in the D39Δ<i>spd1672</i>-treated mice...
March 15, 2018: Canadian Journal of Microbiology
Yawen Li, Fangming Xiu, Zezhong Mou, Zhiwei Xue, Huanhui Du, Chunxue Zhou, Yan Li, Yongyu Shi, Shenyi He, Huaiyu Zhou
AIM: Exosomes are nanoscale membranous vesicles secreted by most cell types able to transfer bioactive molecules among cells, which play crucial roles in intercellular communication. We characterized the exosomes derived from Toxoplasma gondii (T. gondii) and detected the immune response in macrophages. METHODS: We used transmission electron microscopy, nanotracking analysis and western blotting to identify T. gondii exosomes. Functional experiments were performed in RAW264...
March 15, 2018: Nanomedicine
Q N Yu, Y B Guo, X Li, C L Li, W P Tan, X L Fan, Z L Qin, D Chen, W P Wen, S G Zheng, Q L Fu
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. METHODS: The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated...
March 15, 2018: Allergy
Lucyna Kaszubowska, Jerzy Foerster, Jan Jacek Kaczor, Daria Schetz, Tomasz Jerzy Ślebioda, Zbigniew Kmieć
Background: Natural killer cells (NK cells) are cytotoxic lymphocytes of innate immunity that reveal some immunoregulatory properties, however, their role in the process of ageing is not completely understood. The study aimed to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in human NK cells with reference to the process of ageing. Non-stimulated and stimulated with IL-2, LPS or PMA with ionomycin cells originated from peripheral blood samples of: seniors aged over 85 ('the oldest'; n  = 25; 88...
2018: Immunity & Ageing: I & A
Álvaro de Mingo Pulido, Estefanía de Gregorio, Shilpi Chandra, Anna Colell, Albert Morales, Mitchell Kronenberg, Montserrat Marí
Natural killer T (NKT) cells exhibit a specific tissue distribution, displaying the liver the highest NKT/conventional T cell ratio. Upon antigen stimulation, NKT cells secrete Th1 cytokines, including interferon γ (IFNγ), and Th2 cytokines, including IL-4 that recruit and activate other innate immune cells to exacerbate inflammatory responses in the liver. Cysteine cathepsins control hepatic inflammation by regulating κB-dependent gene expression. However, the contribution of cysteine cathepsins other than Cathepsin S to NKT cell activation has remained largely unexplored...
2018: Frontiers in Immunology
Girak Kim, Min Jeong Gu, Soo Ji Kim, Kwang Hyun Ko, Yoon-Chul Kye, Cheol Gyun Kim, Jae-Ho Cho, Woon-Kyu Lee, Ki-Duk Song, Hyuk Chu, Yeong-Min Park, Seung Hyun Han, Cheol-Heui Yun
γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27- γδ T (γδ27- -17) cells. We found selective augmentation of Vγ4+ γδ27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27- -17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli...
2018: Frontiers in Immunology
Chen Zou, Changjing Han, Minjie Zhao, Jingjing Yu, Lin Bai, Yuan Yao, Shuaixin Gao, Hui Cao, Zhi Zheng
Background: Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR. Methods: A proteomic method was used to identify differentially expressed proteins in vitreous humor...
2018: Clinical Proteomics
Justin Stebbing, Kalpit Shah, Lei Cheng Lit, Teresa Gagliano, Angeliki Ditsiou, Tingting Wang, Franz Wendler, Thomas Simon, Krisztina Sára Szabó, Timothy O'Hanlon, Michael Dean, April Camilla Roslani, Swee Hung Cheah, Soo-Chin Lee, Georgios Giamas
Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment...
March 15, 2018: Oncogene
Christopher Wass, Bruno Sauce, Alessandro Pizzo, Louis D Matzel
In both humans and mice, performance on tests of intelligence or general cognitive ability (GCA) is related to dopamine D1 receptor-mediated activity in the prelimbic cortex, and levels of DRD1 mRNA predict the GCA of mice. Here we assessed the turnover rate of D1 receptors as well as the expression level of the D1 chaperone protein (DRiP78) in the medial PPC (mPFC) of mice to determine whether rate of receptor turnover was associated with variations in the GCA of genetically heterogeneous mice. Following assessment of GCA (aggregate performance on four diverse learning tests) mice were administered an irreversible dopamine receptor antagonist (EEDQ), after which the density of new D1 receptors were quantified...
March 14, 2018: Scientific Reports
Liliana L Cubas-Gaona, Elisabet Diaz-Beneitez, Marina Ciscar, José F Rodríguez, Dolores Rodríguez
Infectious bursal disease virus (IBDV) belongs to the Birnaviridae family and is the etiological agent of a highly contagious and immunosuppressive disease (IBD) that affects domestic chickens ( Gallus gallus ). IBD or Gumboro disease leads to high morbidity and mortality of infected animals, and is responsible for major economic losses to the poultry industry world-wide. IBD is characterized by a massive loss of IgM-bearing B lymphocytes and the destruction of the bursa of Fabricius. The molecular bases of the IBDV pathogenicity are still poorly understood, nonetheless, an exacerbated cytokine immune response and B cell depletion due to apoptosis are considered main factors contributing to the severity of the disease...
March 14, 2018: Journal of Virology
Michelle Brault, Tayla M Olsen, Jennifer Martinez, Daniel B Stetson, Andrew Oberst
The sensing of viral nucleic acids within the cytosol is essential for the induction of innate immune responses following infection. However, this sensing occurs within cells that have already been infected. The death of infected cells can be beneficial to the host by eliminating the virus's replicative niche and facilitating the release of inflammatory mediators. In this study, we show that sensing of intracellular DNA or RNA by cGAS-STING or RIG-I-MAVS, respectively, leads to activation of RIPK3 and necroptosis in bone marrow-derived macrophages...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Motoya Murase, Takumi Kawasaki, Rika Hakozaki, Takuya Sueyoshi, Dyaningtyas Dewi Pamungkas Putri, Yuichi Kitai, Shintaro Sato, Masahito Ikawa, Taro Kawai
TLRs recognize pathogen components and drive innate immune responses. They localize at either the plasma membrane or intracellular vesicles such as endosomes and lysosomes, and proper cellular localization is important for their ligand recognition and initiation of signaling. In this study, we disrupted ATP6V0D2, a component of vacuolar-type H+ adenosine triphosphatase (V-ATPase) that plays a central role in acidification of intracellular vesicles, in a macrophage cell line. ATP6V0D2-deficient cells exhibited reduced cytokine production in response to endosome-localized, nucleic acid-sensing TLR3, TLR7, and TLR9, but enhanced inflammatory cytokine production and NF-κB activation following stimulation with LPS, a TLR4 agonist...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Hiroto Kambara, Fei Liu, Xiaoyu Zhang, Peng Liu, Besnik Bajrami, Yan Teng, Li Zhao, Shiyi Zhou, Hongbo Yu, Weidong Zhou, Leslie E Silberstein, Tao Cheng, Mingzhe Han, Yuanfu Xu, Hongbo R Luo
Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT) to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent...
March 13, 2018: Cell Reports
Maryam Ahmadian, Sihao Liu, Shannon M Reilly, Nasun Hah, Weiwei Fan, Eiji Yoshihara, Pooja Jha, C Daniel De Magalhaes Filho, Sandra Jacinto, Andrew V Gomez, Yang Dai, Ruth T Yu, Christopher Liddle, Annette R Atkins, Johan Auwerx, Alan R Saltiel, Michael Downes, Ronald M Evans
Brown adipose tissue (BAT) adaptively transfers energy from glucose and fat into heat by inducing a gene network that uncouples mitochondrial electron transport. However, the innate transcription factors that enable the rapid adaptive response of BAT are unclear. Here, we identify estrogen-related receptor gamma (ERRγ) as a critical factor for maintaining BAT identity. ERRγ is selectively expressed in BAT versus WAT, in which, in the absence of PGC1α, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i...
March 13, 2018: Cell Reports
Peter Moritz Becher, Svenja Hinrichs, Nina Fluschnik, Jan K Hennigs, Karin Klingel, Stefan Blankenberg, Dirk Westermann, Diana Lindner
Heart failure (HF) is a leading cause of morbidity and mortality in the western world. Although optimal medical care and treatment is widely available, the prognosis of patients with HF is still poor. Toll-like receptors (TLRs) are important compartments of the innate immunity. Current studies have identified TLRs as critical mediators in cardiovascular diseases. In the present study, we investigated the involvement of TLRs and interferon (IFN) regulatory factors (IRFs) in different experimental HF models including viral myocarditis, myocardial ischemia, diabetes mellitus, and cardiac hypertrophy...
2018: PloS One
Xiaoyan Wen, Liyan Cui, Seth Morrisroe, Donald Maberry, David R Emlet, Simon C Watkins, Neil A Hukriede, John A Kellum
Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality...
March 14, 2018: American Journal of Physiology. Renal Physiology
Solenn Remy, Karine Kolev-Descamps, Morgane Gossez, Fabienne Venet, Julie Demaret, Etienne Javouhey, Guillaume Monneret
BACKGROUND: While the process of sepsis-induced immunosuppression is now well described in adults, very little information is available on immune functions in pediatric sepsis. The current study investigated this in children with septic shock by performing immunomonitoring, including both innate (monocyte human leukocyte antigen-DR, mHLA-DR, expression) and adaptive immunity (lymphocyte subsets count), as well as cytokine concentrations (IL-6, IL-8, IL-10, IL-1Ra, TNF-α, IFN-γ). Subsequent objectives were to assess the associations between inflammatory response, potential immunosuppression and secondary acquired infection occurrence...
March 13, 2018: Annals of Intensive Care
Aleksandra Klimczak, Urszula Kozlowska, Maciej Kurpisz
Muscular dystrophies represent a group of diseases which may develop in several forms, and severity of the disease is usually associated with gene mutations. In skeletal muscle regeneration and in muscular dystrophies, both innate and adaptive immune responses are involved. The regenerative potential of mesenchymal stem/stromal cells (MSCs) of bone marrow origin was confirmed by the ability to differentiate into diverse tissues and by their immunomodulatory and anti-inflammatory properties by secretion of a variety of growth factors and anti-inflammatory cytokines...
March 13, 2018: Archivum Immunologiae et Therapiae Experimentalis
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