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Embryonic macrophage

Laura E Kuil, Nynke Oosterhof, Samuël N Geurts, Herma C van der Linde, Erik Meijering, Tjakko J van Ham
Microglia are brain resident macrophages, which have specialized functions important in brain development and in disease. They colonize the brain in early embryonic stages, but few factors that drive the migration of yolk sac macrophages (YSMs) into the embryonic brain , or regulate their acquisition of specialized properties are currently known.Here, we present a CRISPR/Cas9-based in vivo reverse genetic screening pipeline to identify new microglia regulators using zebrafish. Zebrafish larvae are particularly suitable due to their external development, transparency and conserved microglia features...
February 14, 2019: Disease Models & Mechanisms
Markus Horsthemke, Lauryl M J Nutter, Anne C Bachg, Boris V Skryabin, Ulrike Honnert, Thomas Zobel, Sven Bogdan, Monika Stoll, Matthias D Seidl, Frank U Mueller, Ursula Ravens, Andreas Unger, Wolfgang A Linke, Pim R R van Gorp, Antoine A F de Vries, Martin Bähler, Peter J Hanley
Whereas myosin 18B (Myo18B) is known to be a critical sarcomeric protein, the function of myosin 18A (Myo18A) is unclear, although it has been implicated in cell motility and Golgi shape. Here we show that homozygous deletion (homozygous tm1a, tm1b or tm1d alleles) of Myo18a in mouse is embryonic lethal. Reminiscent of Myo18b, Myo18a was highly expressed in the embryo heart, and cardiac-restricted Myo18a deletion in mice was embryonic lethal. Surprisingly, using Western blot analysis, we were unable to detect the known isoforms of Myo18A, Myo18Aα and Myo18Aβ, in mouse heart using a custom C-terminal antibody...
February 8, 2019: Journal of Biological Chemistry
Yingxiao Fu, Yihui Wang, Xishuai Tong, Zheng Gong, Xuemin Sun, Jianchang Yuan, Tiantian Zheng, Chuang Li, Dequn Niu, Honggang Dai, Xianfu Liu, Yingji Mao, Baoding Tang, Wei Xue, Yinjiu Huang
This study determined the effects of (E)-3-(2-(4-(3-(2,4-dimethoxyphenyl)acryloyl)phenoxy)ethoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (EDACO) on the differentiation of Gaoyou duck embryonic osteoclasts cultured in vitro. Bone marrow mononuclear cells (BM-MNC) were collected from 23-day-old Gaoyou duck embryos and induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL) in the presence of EDACO at different concentrations (i.e., 10, 20, 40, 80, and 160 µM)...
February 5, 2019: British Poultry Science
Kara J Mould, Nathan D Jackson, Peter M Henson, Max A Seibold, William J Janssen
Macrophages are well-recognized for their dual roles in orchestrating inflammatory responses and regulating tissue repair. In almost all acutely inflamed tissues, two main subclasses of macrophages co-exist. These include embryonically-derived resident tissue macrophages and bone marrow-derived recruited macrophages. While it is clear that macrophage subsets categorized in this fashion display distinct transcriptional and functional profiles, whether all cells within these categories and in the same inflammatory microenvironment share similar functions or whether further specialization exists has not been determined...
February 5, 2019: JCI Insight
Thushari Gunawardana, Khawaja Ashfaque Ahmed, Kalhari Goonewardene, Shelly Popowich, Shanika Kurukulasuriya, Ruwani Karunarathna, Ashish Gupta, Betty Lockerbie, Marianna Foldvari, Suresh K Tikoo, Philip Willson, Susantha Gomis
Oligodeoxynucleotides containing CpG motifs (CpG-ODN) induce innate immunity against bacterial infections. Despite recent advances, how CpG-ODN alone protects against bacterial infections remained elusive. Here, we report for the first time, to our knowledge, that CpG-ODN orchestrates anti-microbial protective immunity by inducing a rapid enrichment of various immune compartments in chickens. In this study, eighteen-day-old embryonated eggs were injected with either 50 µg of CpG-ODN or saline (~n = 90 per group)...
January 23, 2019: Scientific Reports
Gyu Seong Heo, Benjamin Kopecky, Deborah Sultan, Monica Ou, Guoshuai Feng, Geetika Bajpai, Xiaohui Zhang, Hannah Luehmann, Lisa Detering, Yi Su, Florian Leuschner, Christophe Combadière, Daniel Kreisel, Robert J Gropler, Steven L Brody, Yongjian Liu, Kory J Lavine
RATIONALE: Paradigm shifting studies have revealed that the heart contains functionally diverse populations of macrophages derived from distinct embryonic and adult hematopoietic progenitors. Under steady state conditions, the heart is largely populated by CCR2- macrophages of embryonic descent. Following tissue injury, a dramatic shift in macrophage composition occurs whereby CCR2+ monocytes are recruited to the heart and differentiate into inflammatory CCR2+ macrophages that contribute to heart failure progression...
January 21, 2019: Circulation Research
Emmanuel Maes, Irina Sadovskaya, Mathilde Lévêque, Elisabeth Elass-Rochard, Bruno Payré, Thierry Grard, Vassilia Théodorou, Yann Guérardel, Muriel Mercier-Bonin
Lactobacillus farciminis CIP 103136 is a bacterial strain with recognized probiotic properties. However, the mechanisms underlying such properties have only been partially elucidated. In this study, we isolated and purified a cell-wall associated polysaccharide (CWPS), and evaluated its biological role in vitro. The structure of CWPS and responses from stimulation of (i) human macrophage-like THP-1 cells, (ii) human embryonal kidney (HEK293) cells stably transfected with Toll-like receptors (TLR2 or TLR4) and (iii) human colonocyte-like T84 intestinal epithelial cells, upon exposure to CWPS were studied...
January 12, 2019: Glycoconjugate Journal
Jae-Nyoung Heo, Dong-Yeon Kim, Su-Geun Lim, Kiboo Lee, Kyungho Suk, Won-Ha Lee
The functional and physical interaction between mitochondria and the endoplasmic reticulum (ER) has been the subject of intense study. To test the effect of this interaction on macrophage inflammatory activation, the human macrophage-like monocytic leukemia cell line THP-1 was treated with oligomycin, rotenone, or sodium azide, which induce mitochondrial dysfunction (MD) by blocking the electron transport chain (ETC). MD induced by these agents triggered activation of various sensors and markers of ER stress...
January 11, 2019: Cell Biology International
Xiaoping Xie, Jin Jin, Lele Zhu, Zuliang Jie, Yanchuan Li, Baoyu Zhao, Xuhong Cheng, Pingwei Li, Shao-Cong Sun
Background: TRAF3 is known as a central mediator of type I interferon (IFN) induction by various pattern recognition receptors, but the in vivo function of TRAF3 in host defense against viral infection is poorly defined due to the lack of a viable mouse model. Results: Here we show that mice carrying conditional deletion of TRAF3 in myeloid cells or dendritic cells do not have a significant defect in host defense against vesicular stomatitis virus (VSV) infection...
2019: Cell & Bioscience
Davide Bernarreggi, Somayeh Pouyanfard, Dan S Kaufman
Mouse and human pluripotent stem cells have been widely used to study the development of the hematopoietic and immune systems. Although not all cells can be derived with the same efficiency, immune cells such as natural killer (NK) cells and macrophages can be easily produced from PSCs to enable development of new cell-based therapies. NK cells and macrophages are part of the innate immune system, the first line of defense against malignancies and infectious disease. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived NK cells can be produced at a clinical scale suitable for translation into clinical trials...
January 4, 2019: Experimental Hematology
Yingxiao Fu, Yihui Wang, Dequn Niu, Baoding Tang, Yingji Mao, Xishuai Tong, Honggang Dai, Xianfu Liu, Chuang Li, Xuemin Sun, Zheng Gong, Xue Li, Yinjiu Huang, Wei Xue
This study determined the influence of 3-(4-methoxyl)-1-(2-(4-coumarin)prop)-2-en-1-one (MCPEO) on the differentiation of Gaoyou duck embryo osteoclasts cultured in vitro. Bone marrow mononuclear cells (BM-MNCs) were harvested from 23-day-old Gaoyou duck embryos and induced by receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of MCPEO at different concentrations (i.e., 1, 5, 10, 20, and 40 μM). Cell viability measurement, tartrate-resistant acid phosphatase (TRAP) staining, resorption activity assay, and co-staining with Tetramethylrhodamine (TRITC)-conjugated phalloidin and Hoechst 33,258 were conducted...
December 22, 2018: Poultry Science
Isabel Cortegano, Natalia Serrano, Carolina Ruiz, Mercedes Rodríguez, Carmen Prado, Mario Alía, Andrés Hidalgo, Eva Cano, Belén de Andrés, María-Luisa Gaspar
Embryonic megakaryopoiesis starts in the yolk sac on gestational day 7.5 as part of the primitive wave of hematopoiesis, and it continues in the fetal liver when this organ is colonized by hematopoietic progenitors between day 9.5 and 10.5, as the definitive hematopoiesis wave. We characterized the precise phenotype of embryo megakaryocytes in the liver at gestational day 11.5, identifying them as CD41++ CD45- CD9++ CD61+ MPL+ CD42c+ tetraploid cells that express megakaryocyte-specific transcripts and display differential traits when compared to those present in the yolk sac at the same age...
December 20, 2018: Haematologica
Maxim A Nosenko, Anastasia M Moysenovich, Ruslan V Zvartsev, Anastasia Y Arkhipova, Anastasia S Zhdanova, Igor I Agapov, Tamara V Vasilieva, Vladimir G Bogush, Vladimir G Debabov, Sergei A Nedospasov, Mikhail M Moisenovich, Marina S Drutskaya
Despite decades of research, the goal of achieving scarless wound healing remains elusive. One of the approaches, treatment with polymeric microcarriers, was shown to promote tissue regeneration in various in vitro models of wound healing. The in vivo effects of such an approach are attributed to transferred cells with polymeric microparticles functioning merely as inert scaffolds. We aimed to establish a bioactive biopolymer carrier that would promote would healing and inhibit scar formation in the murine model of deep skin wounds...
2018: Frontiers in Immunology
Linxiao Wu, Adrián Magaz, Elizabeth Maughan, Nina Oliver, Arnold Darbyshire, Marilena Loizidou, Mark Emberton, Martin Birchall, Wenhui Song
Increasing evidence suggests the contribution of the dynamic mechanical properties of the extracellular matrix (ECM) to regulate tissue remodeling and regeneration. Following our recent study on a family of thermoresponsive 'stiffness memory' elastomeric nanohybrid scaffolds manufactured via an indirect 3D printing guided thermo-induced phase separation process (3D-TIPS), this work reports in vitro and in vivo cellular responses towards these scaffolds with different initial stiffness and hierarchical interconnected porous structure...
December 14, 2018: Acta Biomaterialia
Esther Francisco, Mehul Suthar, Michael Gale, Amy B Rosenfeld, Vincent R Racaniello
The contributions of RIG-I and MDA5 receptors to sensing viruses of the Picornaviridae family were investigated. The picornaviruses encephalomyocarditis virus (EMCV) and Coxsackievirus B3 (CVB3) are detected by both MDA5 and RIG-I in bone marrow derived macrophages. In macrophages from wild type mice, type I IFN is produced early after infection; IFNβ synthesis is reduced in the absence of each sensor, while IFNα production is reduced in the absence of MDA5. EMCV and CVB3 do not replicate in murine macrophages, and their detection is different in murine embryonic fibroblasts (MEFs), in which the viruses replicate to high titers...
December 11, 2018: Virology
Fatemeh Sharifpanah, Enas Hussein Ali, Maria Wartenberg, Heinrich Sauer
The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and leukopoiesis are interrelated, the effect of Silibinin on leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO)...
December 11, 2018: Phytotherapy Research: PTR
Si Min Lai, Jianpeng Sheng, Pravesh Gupta, Laurent Renia, Kaibo Duan, Francesca Zolezzi, Klaus Karjalainen, Evan W Newell, Christiane Ruedl
Inflammation-induced disappearance of tissue-resident macrophages represents a key pathogen defense mechanism. Using a model of systemic blood-stage malaria, we studied the dynamics of tissue-resident macrophages in multiple organs to determine how they are depleted and refilled during the course of disease. We show that Plasmodium infection results in a transient loss of embryonically established resident macrophages prior to the parasitemia peak. Fate-mapping analysis reveals that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche predominantly through self-renewal...
December 11, 2018: Cell Reports
Kristin Schultz, Christina Grieger Lindner, Yong Li, Pavel Urbánek, Anne Ruschel, Kerstin Minnich, Dunja Bruder, Marcus Gereke, Antonio Sechi, Peter Herrlich
The adhesion molecule and co-receptor of receptor tyrosine kinases, CD44, is expressed in all cells of the immune system, but also in numerous non-immune cells. CD44 plays roles in the cellular response to different pathogens. The molecular actions of CD44 during these processes are by and large still unknown. The CD44 molecule undergoes a sequential proteolytic cleavage which leads to the release of a soluble intracellular domain (CD44-ICD). Previous reports had shown that the CD44-ICD is taken up into the nucleus where it enhances transcription of specific target genes...
2018: PloS One
Fiona M Rudkin, Ingrida Raziunaite, Hillary Workman, Sosthene Essono, Rodrigo Belmonte, Donna M MacCallum, Elizabeth M Johnson, Lisete M Silva, Angelina S Palma, Ten Feizi, Allan Jensen, Lars P Erwig, Neil A R Gow
The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations...
December 11, 2018: Nature Communications
Gulce Itir Percin, Jiri Eitler, Andrea Kranz, Jun Fu, Jeffrey W Pollard, Ronald Naumann, Claudia Waskow
Regulatory mechanisms controlling the pool size of spleen dendritic cells (DC) remain incompletely understood. DCs are continuously replenished from hematopoietic stem cells, and FLT3-mediated signals cell-intrinsically regulate homeostatic expansion of spleen DCs. Here we show that combining FLT3 and CSF1R-deficiencies results in specific and complete abrogation of spleen DCs in vivo. Spatiotemporally controlled CSF1R depletion reveals a cell-extrinsic and non-hematopoietic mechanism for DC pool size regulation...
December 11, 2018: Nature Communications
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