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https://www.readbyqxmd.com/read/29681904/brain-resident-microglia-and-blood-borne-macrophages-orchestrate-central-nervous-system-inflammation-in-neurodegenerative-disorders-and-brain-cancer
#1
REVIEW
Lisa Sevenich
Inflammation is a hallmark of different central nervous system (CNS) pathologies. It has been linked to neurodegenerative disorders as well as primary and metastatic brain tumors. Microglia, the brain-resident immune cells, are emerging as a central player in regulating key pathways in CNS inflammation. Recent insights into neuroinflammation indicate that blood-borne immune cells represent an additional critical cellular component in mediating CNS inflammation. The lack of experimental systems that allow for discrimination between brain-resident and recruited myeloid cells has previously halted functional analysis of microglia and their blood-borne counterparts in brain malignancies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29680179/progress-in-understanding-the-pathophysiology-of-multiple-sclerosis
#2
REVIEW
H Zéphir
Multiple sclerosis (MS) arises in people who have a genetic susceptibility to environmental factors and events, which ultimately trigger the disease. It is thought that peripheral immune cells are mobilized and enter the CNS through the impaired blood-brain barrier in the subarachnoid space, as acute lesions show large numbers of macrophages and CD8+ T cells and, to a lesser extent, CD4+ T cells, B cells and plasma cells. Demyelination is mostly localized to focal lesions in early relapsing-remitting (RR) MS, whereas other areas of white matter appear normal...
April 18, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29679380/a-non-myeloablative-chimeric-mouse-model-accurately-defines-microglia-and-macrophage-contribution-in-glioma
#3
Kenny Yu, A Saam Youshani, Fiona L Wilkinson, Claire O'Leary, Peter Cook, Liisi Laaniste, Aiyin Liao, Dominic Mosses, Christopher Waugh, Hannah Shorrock, Omar Pathmanaban, Andrew Macdonald, Ian Kamaly-Asl, Federico Roncaroli, Brian W Bigger
AIMS: Resident and peripherally-derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion, and attenuating host immune responses. Differentiating these cells' origins is challenging and current pre-clinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel non-myeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation...
April 20, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29679057/a-legionella-pneumophila-amylase-is-essential-for-intracellular-replication-in-human-macrophages-and-amoebae
#4
Ashley Best, Christopher Price, Mateja Ozanic, Marina Santic, Snake Jones, Yousef Abu Kwaik
Legionella pneumophila invades protozoa with an "accidental" ability to cause pneumonia upon transmission to humans. To support its nutrition during intracellular residence, L. pneumophila relies on host amino acids as the main source of carbon and energy to feed the TCA cycle. Despite the apparent lack of a requirement for glucose for L. pneumophila growth in vitro and intracellularly, the organism contains multiple amylases, which hydrolyze polysaccharides into glucose monomers. Here we describe one predicted putative amylase, LamB, which is uniquely present only in L...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674348/rkip-mediates-autoimmune-inflammation-by-positively-regulating-il-17r-signaling
#5
Wenlong Lin, Ning Wang, Kangxing Zhou, Fasheng Su, Yu Jiang, Jianan Shou, Huan Liu, Chunmei Ma, Youchun Qian, Kai Wang, Xiaojian Wang
Th17 cells contribute to the development of autoimmune diseases by secreting interleukin-17 (IL-17), which activates its receptor (IL-17R) that is expressed on epithelial cells, macrophages, microglia, and resident neuroectodermal cells. However, the mechanisms through which IL-17R-mediated signaling contributes to the development of autoimmune disease have not been completely elucidated. Here, we demonstrate that Raf-1 kinase inhibitor protein (RKIP) deficiency in mice ameliorates the symptoms of experimental autoimmune encephalomyelitis (EAE)...
April 19, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29670921/roles-of-macrophage-subtypes-in-bowel-anastomotic-healing-and-anastomotic-leakage
#6
REVIEW
Jinyao Shi, Zhouqiao Wu, Ziyu Li, Jiafu Ji
Macrophages play an important role in host defense, in addition to the powerful ability to phagocytose pathogens or foreign matters. They fulfill a variety of roles in immune regulation, wound healing, and tissue homeostasis preservation. Macrophages are characterized by high heterogeneity, which can polarize into at least two major extremes, M1-type macrophages (classical activation) which are normally derived from monocytes and M2-type macrophages (alternative activation) which are mostly those tissue-resident macrophages...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29670919/dysregulated-functions-of-lung-macrophage-populations-in-copd
#7
REVIEW
Theodore S Kapellos, Kevin Bassler, Anna C Aschenbrenner, Wataru Fujii, Joachim L Schultze
Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#8
Linnéa La Fleur, Vanessa F Boura, Andrey Alexeyenko, Anders Berglund, Victor Pontén, Johanna Sm Mattsson, Dijana Djureinovic, Johan Persson, Hans Brunnström, Johan Isaksson, Eva Brandén, Hirsh Koyi, Patrick Micke, Mikael Ci Karlsson, Johan Botling
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29666944/macrophages-play-an-essential-role-in-trauma-induced-sterile-inflammation-and-tissue-repair
#9
REVIEW
Moritz Peiseler, Paul Kubes
Severe trauma is accompanied by a profound activation of the immune system. Patients with polytrauma develop systemic inflammatory response syndrome (SIRS) and often sepsis, which contributes substantially to high mortality of this condition. On a cellular level, necrosis and loss of plasma membrane integrity lead to the release of endogenous "damage-associated molecular patterns" (DAMPs) as danger signals, which in turn activate innate immune cells. Inflammation that occurs in the absence of invading pathogens has been termed sterile inflammation and trauma with tissue damage represents an acute form of sterile inflammation...
April 17, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/29666241/muscularis-macrophage-development-in-the-absence-of-an-enteric-nervous-system
#10
Marina Avetisyan, Julia E Rood, Silvia Huerta Lopez, Rajarshi Sengupta, Elizabeth Wright-Jin, Joseph D Dougherty, Edward M Behrens, Robert O Heuckeroth
The nervous system of the bowel regulates the inflammatory phenotype of tissue resident muscularis macrophages (MM), and in adult mice, enteric neurons are the main local source of colony stimulating factor 1 (CSF1), a protein required for MM survival. Surprisingly, we find that during development MM colonize the bowel before enteric neurons. This calls into question the requirement for neuron-derived CSF1 for MM colonization of the bowel. To determine if intestinal innervation is required for MM development, we analyzed MM of neonatal Ret -/- ( Ret KO) mice that have no enteric nervous system in small bowel or colon...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29662171/fatal-demyelinating-disease-is-induced-by-monocyte-derived-macrophages-in-the-absence-of-tgf-%C3%AE-signaling
#11
Harald Lund, Melanie Pieber, Roham Parsa, David Grommisch, Ewoud Ewing, Lara Kular, Jinming Han, Keying Zhu, Jik Nijssen, Eva Hedlund, Maria Needhamsen, Sabrina Ruhrmann, André Ortlieb Guerreiro-Cacais, Rasmus Berglund, Maria J Forteza, Daniel F J Ketelhuth, Oleg Butovsky, Maja Jagodic, Xing-Mei Zhang, Robert A Harris
The cytokine transforming growth factor-β (TGF-β) regulates the development and homeostasis of several tissue-resident macrophage populations, including microglia. TGF-β is not critical for microglia survival but is required for the maintenance of the microglia-specific homeostatic gene signature1,2 . Under defined host conditions, circulating monocytes can compete for the microglial niche and give rise to long-lived monocyte-derived macrophages residing in the central nervous system (CNS)3-5 . Whether monocytes require TGF-β for colonization of the microglial niche and maintenance of CNS integrity is unknown...
April 16, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29661474/the-role-of-hepatic-macrophages-in-liver-metastasis
#12
Jiri Keirsse, Helena Van Damme, Xenia Geeraerts, Alain Beschin, Geert Raes, Jo A Van Ginderachter
The liver is a major target organ for metastasis of both gastrointestinal and extra-gastrointestinal cancers. Due to its frequently inoperable nature, liver metastasis represents a leading cause of cancer-associated death worldwide. In the past years, the pivotal role of the immune system in this process is being increasingly recognised. In particular, the role of the hepatic macrophages, both recruited monocyte-derived macrophages (Mo-Mfs) and tissue-resident Kupffer cells (KCs), has been shown to be more versatile than initially imagined...
April 6, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29660372/heparan-sulfate-3-o-sulfotransferase-2-hs3st2-displays-an-unexpected-subcellular-localization-in-the-plasma-membrane
#13
Maxime Delos, François Foulquier, Charles Hellec, Dorothée Vicogne, Alexandre Fifre, Mathieu Carpentier, Dulce Papy-Garcia, Fabrice Allain, Agnès Denys
BACKGROUND: Heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-O-sulfotransferases (HS3STs) in humans, still it is the rarest modification in HS and its biological function is yet misunderstood. HS3ST2 and HS3ST3B exhibit the same activity in vitro. They are however differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes. Here, we hypothesized that both isozymes might also display distinct subcellular localizations...
April 13, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29655887/engineering-riboswitch-in-l-major-from-prediction-to-conceptualization
#14
Pruthvi Raj Bejugam, Shailza Singh
Post-transcriptional gene regulation is a vital process to regulate expression of the key genes in the eukaryotic cell. Such processes are essential for pathogens which reside inside the host cell. One such pathogen is Leishmania major, which causes cutaneous leishmaniasis. The parasite lives inside the macrophages of mammalian host (mostly human). Inside the macrophage, Leishmania genes show complex host-pathogen interaction regulating a plethora of gene expression. Till date, most of the studies have shown this kind of regulation with respect to the host macrophages...
April 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29650244/heart-macrophages-and-dendritic-cells-in-sickness-and-in-health-a-tale-of-a-complicated-marriage
#15
Katrien Van der Borght, Bart N Lambrecht
Heart disease is the major cause of death and it is broadly recognized that the immune system plays a central role in healthy and injured heart. Here, we focus on the contribution of various subsets of mononuclear phagocytes in the cardiac system. Macrophages and dendritic cells reside in the healthy myocardium to fulfill homeostatic functions and rapidly increase in numbers in diseases like myocardial ischemia and myocarditis to contribute to disease or resolve it. Recent experiments have revealed the extraordinary heterogeneity of cardiac mononuclear phagocytes that differ in origin, lifespan, phenotype and function...
April 5, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29650243/testicular-macrophages-guardians-of-fertility
#16
Noushin Mossadegh-Keller, Michael H Sieweke
Macrophages are innate immune cells present in essentially every organ of the body with dedicated tissue specific functions. We will present in this review the unique properties and functions of macrophage populations residing in the testis, an immune-privileged organ. Testicular macrophages (tMΦ) could be seen as guardians of fertility due to their immunosuppressive functions protecting spermatogenesis from auto immune-attack. They exhibit testis specific functions with essential roles in normal testis homeostasis and fetal testicular development...
April 3, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29644573/myeloid-specific-targeting-of-notch-ameliorates-murine-renal-fibrosis-via-reduced-infiltration-and-activation-of-bone-marrow-derived-macrophage
#17
Yali Jiang, Yuanyuan Wang, Pengfei Ma, Dongjie An, Junlong Zhao, Shiqian Liang, Yuchen Ye, Yingying Lu, Peng Zhang, Xiaowei Liu, Hua Han, Hongyan Qin
Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β...
April 11, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29643512/innate-immune-memory-in-the-brain-shapes-neurological-disease-hallmarks
#18
Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani, Michael Gertig, Thomas Ulas, Gaurav Jain, Jessica Wagner, Lisa M Häsler, Katleen Wild, Angelos Skodras, Thomas Blank, Ori Staszewski, Moumita Datta, Tonatiuh Pena Centeno, Vincenzo Capece, Md Rezaul Islam, Cemil Kerimoglu, Matthias Staufenbiel, Joachim L Schultze, Marc Beyer, Marco Prinz, Mathias Jucker, André Fischer, Jonas J Neher
Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29643192/characterizing-the-mechanisms-of-nonopsonic-uptake-of-cryptococci-by-macrophages
#19
Jenson Lim, Christopher J Coates, Paula I Seoane, Mariam Garelnabi, Leanne M Taylor-Smith, Pauline Monteith, Camille L Macleod, Claire J Escaron, Gordon D Brown, Rebecca A Hall, Robin C May
The pathogenic fungus Cryptococcus enters the human host via inhalation into the lung and is able to reside in a niche environment that is serum- (opsonin) limiting. Little is known about the mechanism by which nonopsonic phagocytosis occurs via phagocytes in such situations. Using a combination of soluble inhibitors of phagocytic receptors and macrophages derived from knockout mice and human volunteers, we show that uptake of nonopsonized Cryptococcus neoformans and C. gattii via the mannose receptor is dependent on macrophage activation by cytokines...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29642434/a-single-dose-of-atorvastatin-applied-acutely-after-spinal-cord-injury-suppresses-inflammation-apoptosis-and-promotes-axon-outgrowth-which-might-be-essential-for-favorable-functional-outcome
#20
Katarina Bimbova, Maria Bacova, Alexandra Kisucka, Jaroslav Pavel, Jan Galik, Peter Zavacky, Martin Marsala, Andrea Stropkovska, Jana Fedorova, Stefania Papcunova, Jana Jachova, Nadezda Lukacova
The aim of our study was to limit the inflammatory response after a spinal cord injury (SCI) using Atorvastatin (ATR), a potent inhibitor of cholesterol biosynthesis. Adult Wistar rats were divided into five experimental groups: one control group, two Th9 compression (40 g/15 min) groups, and two Th9 compression + ATR (5 mg/kg, i.p.) groups. The animals survived one day and six weeks. ATR applied in a single dose immediately post-SCI strongly reduced IL-1β release at 4 and 24 h and considerably reduced the activation of resident cells at one day post-injury...
April 7, 2018: International Journal of Molecular Sciences
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