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Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 9, 2018: Immunity
Lei Zhang, Jie Ren, Peidian Shi, Dong Lu, Chengxue Zhao, Yanxin Su, Lilin Zhang, Jinhai Huang
B4GALT5, also known as β-1, 4 galactosyltransferase V, is one of the members of β-1, 4 galactosyltransferase gene (B4GALT) family, which was concerned with embryonic development, tumor generation, other malignant diseases. In this study, we firstly cloned porcine B4GALT (pB4GALT5) from porcine alveolar macrophages, and predicted the structural domain and function of seven porcine β-1, 4 galactosyltransferase (I-VII) based on transcriptome analysis of PRRSV infected cells. Additionally, the upregulated porcine B4GALT5 expression was detected from PRRSV infected porcine alveolar macrophage (PAM) cells...
2018: Frontiers in Cellular and Infection Microbiology
Giulia Cisbani, Audrey Le Behot, Marie-Michèle Plante, Paul Préfontaine, Manon Lecordier, Serge Rivest
Stroke is the second cause of mortality worldwide and occurs following the interruption of cerebral blood circulation by cerebral vessel burst or subsequent to a local thrombus formation. Ischemic lesion triggers an important inflammatory response, characterized by massive infiltration of leukocytes, activation of glial cells and neurovascular reorganization. Chemokines and their receptors, such as CCR2 and CX3CR1, play an important role in leukocyte recruitment in the damaged area. Mice genetically depleted for the two receptors CCR2 and CX3CR1 underwent focal cerebral ischemia, based on the topical application of ferric chloride to truncate the distal middle cerebral artery...
March 12, 2018: Brain, Behavior, and Immunity
Kurt A Zimmerman, Cheng Jack Song, Nancy Gonzalez-Mize, Zhang Li, Bradley K Yoder
Hepatorenal fibrocystic disease (HRFCD) is characterized by cysts in the kidney and liver with associated fibrosis and is the result of defects in proteins required for cilia function or assembly. Previous reports indicate that macrophages, mainly M2-like macrophages, contribute to HRFCD, although the origin (yolk-sac derived resident macrophages vs bone-marrow derived infiltrating macrophages) and contribution of these cells to the observed phenotypes is unknown. Herein, we utilize a congenital model of cilia dysfunction (IFT88Orpk ) to study the importance of macrophages in HRFCD...
March 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Manjula Karpurapu, Yong Gyu Lee, Ziqing Qian, Jin Wen, Megan N Ballinger, Luiza Rusu, Sangwoon Chung, Jing Deng, Feng Qian, Brenda F Reader, Teja Srinivas Nirujogi, Gye Young Park, Dehua Pei, John W Christman
Specific therapies targeting cellular and molecular events of sepsis induced Acute Lung Injury (ALI) pathogenesis are lacking. We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression. Mouse pulmonary microvascular endothelial cell monolayer maintained a tighter barrier function when co-cultured with LPS stimulated NFATc3 deficient macrophages whereas wild type macrophages caused leaky monolayer barrier...
February 13, 2018: Oncotarget
Stefan Gahbauer, Kristyna Pluhackova, Rainer A Böckmann
Chemokine receptors, a subclass of G protein coupled receptors (GPCRs), play essential roles in the human immune system, they are involved in cancer metastasis as well as in HIV-infection. A plethora of studies show that homo- and heterodimers or even higher order oligomers of the chemokine receptors CXCR4, CCR5, and CCR2 modulate receptor function. In addition, membrane cholesterol affects chemokine receptor activity. However, structural information about homo- and heterodimers formed by chemokine receptors and their interplay with cholesterol is limited...
March 12, 2018: PLoS Computational Biology
Dieter Adelmann, Leonie Bicknell, Claus U Niemann, John Feiner, Garrett R Roll, Lyle Burdine, Elizabeth L Whitlock
BACKGROUND: During kidney transplantation, intraoperative fluid management can affect post-transplant graft function. It is unclear whether or not central venous pressure (CVP) monitoring is required to guide fluid therapy during kidney transplantation. METHODS: We compared post-transplant graft function in recipients of living donor kidney transplants between August 2006 and March 2009 based on the use or absence of intraoperative CVP monitoring. Graft function, assessed using the creatinine reduction ratio on postoperative day 2 (CCR2), was evaluated by multivariable linear regression analysis and in a propensity-matched cohort...
March 11, 2018: Clinical Transplantation
Petr Dubový, Ilona Klusáková, Ivana Hradilová-Svíženská, Marek Joukal, Pere Boadas-Vaello
Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM)...
2018: Frontiers in Cellular Neuroscience
Hebatullah Laban, Andreas Weigert, Joana Zink, Amro Elgheznawy, Christoph Schürmann, Lea Günther, Randa Abdel Malik, Sabrina Bothur, Susanne Wingert, Rolf Bremer, Michael A Rieger, Bernhard Brüne, Ralf P Brandes, Ingrid Fleming, Peter M Benz
In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP-/- mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair...
March 5, 2018: Journal of Cell Biology
Eanna P Connaughton, Serika Naicker, Shirley A Hanley, Stephanie M Slevin, John K Eykelenboom, Noel F Lowndes, Timothy O'Brien, Rhodri Ceredig, Matthew D Griffin, Michael C Dennedy
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults...
March 5, 2018: Immunology and Cell Biology
Liang Liu, Lin Yang, Wei Yan, Jing Zhai, Donald Pizzo, Peiguo Chu, Andrew R Chin, Meng Shen, Chuan Dong, Xianhui Ruan, Xiubao Ren, George Somlo, Shizhen Emily Wang
PURPOSE: Preoperative or neoadjuvant therapy (NT) is increasingly used in patients with locally advanced or inflammatory breast cancer (BC) to allow optimal surgery and aim for pathological response. However, many BCs are resistant or relapse after treatment. Here, we investigated conjunctive chemotherapy-triggered events occurring systemically and locally, potentially promoting a cancer stem-like cell (CSC) phenotype and contributing to tumor relapse. EXPERIMENTAL DESIGN: We started by comparing the effect of paired pre- and post-NT patient sera on the CSC properties of BC cells...
March 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yanping Tong, Tao Yang, Jingwen Wang, Tianyou Zhao, Lei Wang, Yuezhi Kang, Cuicui Cheng, Yongping Fan
Background: A prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission...
2018: Frontiers in Neurology
Lindsey A Muir, Samadhi Kiridena, Cameron Griffin, Jennifer B DelProposto, Lynn Geletka, Gabriel Martinez-Santibañez, Brian F Zamarron, Hannah Lucas, Kanakadurga Singer, Robert W O' Rourke, Carey N Lumeng
Obesity-related changes in adipose tissue leukocytes, in particular adipose tissue macrophages (ATMs) and dendritic cells (ATDCs), are implicated in metabolic inflammation, insulin resistance, and altered regulation of adipocyte function. We evaluated stromal cell and white adipose tissue (WAT) expansion dynamics with high fat diet (HFD) feeding for 3-56 days, quantifying ATMs, ATDCs, endothelial cells (ECs), and preadipocytes (PAs) in visceral epididymal WAT and subcutaneous inguinal WAT. To better understand mechanisms of the early response to obesity, we evaluated ATM proliferation and lipid accumulation...
March 1, 2018: Journal of Leukocyte Biology
Lei Chen, Gao-Qin Liu, Hong-Ya Wu, Ji Jin, Xue Yin, Dan Li, Pei-Rong Lu
AIM: To explore the interaction between macrophages and chemokines [monocyte chemoattractant protein 1 (MCP-1/CCL2) and fractalkine/CX3CL1] and the effects of their interaction on neovascularization. METHODS: Human peripheral blood mononuclear cells, donated by healthy volunteers, were separated and cultured in RPMI-1640 medium containing 10% fetal bovine serum, then induced into macrophages by stimulation with 30 µg/L granulocyte macrophage-colony stimulating factor (GM-CSF)...
2018: International Journal of Ophthalmology
François Huaux, Valentin De Gussem, Astrid Lebrun, Yousof Yakoub, Mihaly Palmai-Pallag, Saloua Ibouraadaten, Francine Uwambayinema, Dominique Lison
Occupational exposure to indium tin oxide (ITO) particles has been associated with the development of severe lung diseases, including pulmonary alveolar proteinosis (PAP). The mechanisms of this lung toxicity remain unknown. Here, we reveal the respective roles of resident alveolar (Siglec-Fhigh AM) and recruited interstitial (Siglec-Flow IM) macrophages contributing in concert to the development of PAP. In mice treated with ITO particles, PAP is specifically associated with IL-1α (not GM-CSF) deficiency and Siglec-Fhigh AM (not Siglec-Flow IM) depletion...
February 26, 2018: Archives of Toxicology
Shu-Hung Huang, Sheng-Hua Wu, Su-Shin Lee, Yun-Nan Lin, Chee-Yin Chai, Chung-Sheng Lai, Hui-Min David Wang
Objective: No effective treatments have yet been developed for burn-induced neuropathic pain. Platelet-rich plasma (PRP) has been reported to ameliorate various types of inflammation pain. However, the effect of PRP on burn-induced neuropathic pain is unclear. Methods: Burn-induced neuropathic pain Sprague-Dawley rat model was confirmed using a mechanical response test 4 weeks after the burn injuries were sustained, following which PRP was injected in the scar area. The rats were divided into four groups (n = 6) as following: Group A, Sham; Group B, Sham + PRP; Group C, Burn; and Group D, Burn + PRP...
2018: International Journal of Medical Sciences
Chang Hoon Lee, Hongwei H Zhang, Satya P Singh, Lily Koo, Juraj Kabat, Hsinyi Tsang, Tej Pratap Singh, Joshua M Farber
Many mediators and regulators of extravasation by bona fide human memory-phenotype T cells remain undefined. Mucosal-associated invariant T (MAIT) cells are innate-like, anti-bacterial cells that we found excelled at crossing inflamed endothelium. They displayed abundant selectin ligands, with high expression of FUT7 and ST3GAL4 , and expressed CCR6, CCR5, and CCR2, which played non-redundant roles in trafficking on activated endothelial cells. MAIT cells selectively expressed CCAAT/enhancer-binding protein delta (C/EBPδ)...
February 22, 2018: ELife
Remo Castro Russo, Benedetta Savino, Massimiliano Mirolo, Chiara Buracchi, Giovanni Germano, Achille Anselmo, Luca Zammataro, Fabio Pasqualini, Alberto Mantovani, Massimo Locati, Mauro M Teixeira
RATIONALE: Chemokines coordinate lung inflammation and fibrosis by acting on chemokine receptors expressed on leukocytes and other cell types. Atypical chemokine receptors (ACKRs) bind, internalize and degrade chemokines, tuning homeostasis and immune responses. ACKR2 recognizes and decreases levels of inflammatory CC chemokines. The role of ACKR2 in fibrogenesis is unknown. OBJECTIVE: Investigate the role of ACKR2 in the context of pulmonary fibrosis. METHODS: The effects of ACKR2 expression and deficiency during inflammation and fibrosis were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone marrow chimeras and antibody-mediated leukocyte depletion...
February 22, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Bridget S Fisher, Richard R Green, Rachel R Brown, Matthew P Wood, Tiffany Hensley-McBain, Cole Fisher, Jean Chang, Andrew D Miller, William J Bosche, Jeffrey D Lifson, Maud Mavigner, Charlene J Miller, Michael Gale, Guido Silvestri, Ann Chahroudi, Nichole R Klatt, Donald L Sodora
Liver disease is a leading contributor to morbidity and mortality during HIV infection, despite the use of combination antiretroviral therapy (cART). The precise mechanisms of liver disease during HIV infection are poorly understood partially due to the difficulty in obtaining human liver samples as well as the presence of confounding factors (e.g. hepatitis co-infection, alcohol use). Utilizing the simian immunodeficiency virus (SIV) macaque model, a controlled study was conducted to evaluate the factors associated with liver inflammation and the impact of cART...
February 21, 2018: PLoS Pathogens
Alina Wiesemann, Julia Ketteler, Alexis Slama, Florian Wirsdörfer, Thomas Hager, Katharina Roeck, Daniel Engel, Jens Fischer, Clemens Aigner, Verena Jendrossek, Diana Klein
AIMS: Radiation-induced normal tissue toxicity often precludes the application of curative radiation doses. Here we investigated the therapeutic potential of Ccl2 signaling inhibition to protect normal lung tissue from radiotherapy (RT)-induced injury. RESULTS: RT-induced vascular dysfunction and associated adverse effects can be efficiently antagonized by inhibition of Ccl2 signaling using either the selective Ccl2 inhibitor bindarit (BIN) or mice deficient for the main Ccl2 receptor CCR2 (KO)...
February 20, 2018: Antioxidants & Redox Signaling
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