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Mariah L Hoye, Angela S Archambault, Taylor M Gordon, Landon K Oetjen, Matthew D Cain, Robyn S Klein, Seth D Crosby, Brian S Kim, Timothy M Miller, Gregory F Wu
Innate immune cells are integral to the pathogenesis of several diseases of the central nervous system (CNS), including multiple sclerosis (MS). Dendritic cells (DCs) are potent CD11c+ antigen-presenting cells that are critical regulators of adaptive immune responses, particularly in autoimmune diseases such as MS. The regulation of DC function in both the periphery and CNS compartment has not been fully elucidated. One limitation to studying the role of CD11c+ DCs in the CNS is that microglia can upregulate CD11c during inflammation, making it challenging to distinguish bone marrow-derived DCs (BMDCs) from microglia...
May 10, 2018: Immunology
R M Martinez, V Fattori, P Saito, C B P Melo, S M Borghi, I C Pinto, A J C Bussmann, M M Baracat, S R Georgetti, W A Verri, R Casagrande
BACKGROUND: Lipoxin A4 (LXA4 ) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation. OBJECTIVE: To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. METHODS: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4...
April 27, 2018: Journal of Dermatological Science
A A Igolkina, Yu B Porozov, E P Chizhevskaya, E E Andronov
Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF) of Rhizobium leguminosarum bv. viciae , were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We carried out this analysis based on the hypothesis that in a contact zone of two docked components (proteins or ligands) the population polymorphism or conservatism is mutual, i...
2018: Frontiers in Plant Science
Matthew A Jorgenson, Kevin D Young
While screening the Pfam database for novel peptidoglycan (PG) binding modules, we identified the OapA domain, which is annotated to be a LysM-like domain. LysM domains bind PG and mediate localization to the septal ring. In the Gram-negative bacterium Escherichia coli , an OapA domain is present in YtfB, an inner membrane protein of unknown function but whose overproduction causes cells to filament. Together, these observations suggested that YtfB directly affects cell division, most likely through its OapA domain...
April 23, 2018: Journal of Bacteriology
Girija Goyal, Karrie Wong, Christopher J Nirschl, Nicholas Souders, Donna Neuberg, Niroshana Anandasabapathy, Glenn Dranoff
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T cells (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both immune tolerance and protection, but the role of PPARγ in these pathways is poorly understood. Here we reveal an unexpected stimulatory role for PPARγ in the generation of antitumor immunity with irradiated, GM-CSF-secreting tumor-cell vaccines (GVAX)...
April 18, 2018: Cancer Immunology Research
Yogesh Saini, Brandon W Lewis, Dongfang Yu, Hong Dang, Alessandra Livraghi-Butrico, Fabio Del Piero, Wanda K O'Neal, Richard C Boucher
Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial MΦ-deficiency was crossed with the Scnn1b-Tg mouse model of CB and the progenies were studied at 4-5 weeks of age...
April 2018: Physiological Reports
Zhe Zhou, Yi Tian, Peihua Cong, Yanmin Zhu
Apple gene, MD09G1111800, was identified as a chitin binding receptor-like kinase based on sequence similarity to AtCERK1 (chitin elicitor receptor kinase 1) from Arabidopsis. Sequence analysis on genomic structure, domain composition and transcriptional response to exogenous chitin treatment indicated that MD09G1111800 is an ortholog to AtCERK1 and was therefore named as MdCERK1. Tissue specific expression patterns indicated that MdCERK1 is primarily functional in vegetative tissues of leaf and root, rather than flower, fruit and seed of apple plant...
April 2018: Plant Science: An International Journal of Experimental Plant Biology
Céline Caravagna, Alexandre Jaouën, Sophie Desplat-Jégo, Keith K Fenrich, Elise Bergot, Hervé Luche, Pierre Grenot, Geneviève Rougon, Marie Malissen, Franck Debarbieux
In both multiple sclerosis and its model experimental autoimmune encephalomyelitis (EAE), the extent of resident microglia activation and infiltration of monocyte-derived cells to the CNS is positively correlated to tissue damage. To address the phenotype characterization of different cell subsets, their spatio-temporal distributions and contributions to disease development we induced EAE in Thy1-CFP//LysM-EGFP//CD11c-EYFP reporter mice. We combined high content flow cytometry, immunofluorescence and two-photon imaging in live mice and identified a stepwise program of inflammatory cells accumulation...
March 23, 2018: Scientific Reports
Peter Mancuso, Jeffrey L Curtis, Christine M Freeman, Marc Peters-Golden, Jason B Weinberg, Martin G Myers
Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiologic functions including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia...
March 22, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Frederick A Rubino, Sujeet Kumar, Natividad Ruiz, Suzanne Walker, Daniel Kahne
MurJ, the flippase that exports the bacterial cell wall mon-omer Lipid II to the periplasm, is a target for new antibiot-ics, which are desperately needed to treat Gram-negative infections. Quantitative methods to monitor MurJ activity are required to characterize inhibitors but are challenging to develop because the lipid-linked substrate is not chemi-cally altered in a flippase reaction. Here we show that MurJ inhibition can be quantified by measuring the accu-mulation of intracellular Lipid II using a biotin-tagging strategy...
March 20, 2018: Journal of the American Chemical Society
Ariel Molly Wilson, Zhuo Shao, Vanessa Grenier, Gaëlle Mawambo, Jean-François Daudelin, Agnieszka Dejda, Frédérique Pilon, Natalija Popovic, Salix Boulet, Célia Parinot, Malika Oubaha, Nathalie Labrecque, Vincent de Guire, Mathieu Laplante, Guillaume Lettre, Florian Sennlaub, Jean-Sebastien Joyal, Michel Meunier, Przemyslaw Sapieha
Obesity gives rise to metabolic complications by mechanisms that are poorly understood. Although chronic inflammatory signaling in adipose tissue is typically associated with metabolic deficiencies linked to excessive weight gain, we identified a subset of neuropilin-1 (NRP1)-expressing myeloid cells that accumulate in adipose tissue and protect against obesity and metabolic syndrome. Ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages toward a more inflammatory glycolytic metabolism...
March 16, 2018: Science Immunology
Tom Zortel, Annette Schmitt-Graeff, Susanne Kirschnek, Georg Häcker
Background: Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown, but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Methods: Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of B-cell lymphoma 2 (Bcl-2) in hematopoietic cells (Bcl-2 mice), and mice where mature neutrophils are lacking due to the deletion of Myeloid cell leukemia 1 (Mcl-1) in myeloid cells (LysM-cre-mcl-1-flox mice; Mcl-1 mice)...
May 5, 2018: Journal of Infectious Diseases
Sharmila Nair, Jeremy P Huynh, Vicky Lampropoulou, Ekaterina Loginicheva, Ekaterina Esaulova, Anshu P Gounder, Adrianus C M Boon, Elizabeth A Schwarzkopf, Tara R Bradstreet, Brian T Edelson, Maxim N Artyomov, Christina L Stallings, Michael S Diamond
Immune-Responsive Gene 1 (Irg1) is a mitochondrial enzyme that produces itaconate under inflammatory conditions, principally in cells of myeloid lineage. Cell culture studies suggest that itaconate regulates inflammation through its inhibitory effects on cytokine and reactive oxygen species production. To evaluate the functions of Irg1 in vivo, we challenged wild-type (WT) and Irg1 -/- mice with Mycobacterium tuberculosis ( Mtb ) and monitored disease progression. Irg1 -/- , but not WT, mice succumbed rapidly to Mtb , and mortality was associated with increased infection, inflammation, and pathology...
April 2, 2018: Journal of Experimental Medicine
Christine C Yokoyama, Megan T Baldridge, Daisy W Leung, Guoyan Zhao, Chandni Desai, Ta-Chiang Liu, Vladimir E Diaz-Ochoa, Jeremy P Huynh, Jacqueline M Kimmey, Erica L Sennott, Camaron R Hole, Rachel A Idol, Sunmin Park, Kelly M Storek, Caihong Wang, Seungmin Hwang, Ashley Viehmann Milam, Eric Chen, Tobias Kerrinnes, Michael N Starnbach, Scott A Handley, Indira U Mysorekar, Paul M Allen, Denise M Monack, Mary C Dinauer, Tamara L Doering, Renee M Tsolis, Jonathan E Dworkin, Christina L Stallings, Gaya K Amarasinghe, Craig A Micchelli, Herbert W Virgin
Germline-encoded receptors recognizing common pathogen-associated molecular patterns are a central element of the innate immune system and play an important role in shaping the host response to infection. Many of the innate immune molecules central to these signaling pathways are evolutionarily conserved. LysMD3 is a novel molecule containing a putative peptidoglycan-binding domain that has orthologs in humans, mice, zebrafish, flies, and worms. We found that the lysin motif (LysM) of LysMD3 is likely related to a previously described peptidoglycan-binding LysM found in bacteria...
April 20, 2018: Journal of Biological Chemistry
Karl T Debiec, Matthew J Whitley, Leonardus M I Koharudin, Lillian T Chong, Angela M Gronenborn
Multidomain proteins with two or more independently folded functional domains are prevalent in nature. Whereas most multidomain proteins are linked linearly in sequence, roughly one-tenth possess domain insertions where a guest domain is implanted into a loop of a host domain, such that the two domains are connected by a pair of interdomain linkers. Here, we characterized the influence of the interdomain linkers on the structure and dynamics of a domain-insertion protein in which the guest LysM domain is inserted into a central loop of the host CVNH domain...
February 27, 2018: Biophysical Journal
Soichi Sano, Kosei Oshima, Ying Wang, Susan MacLauchlan, Yasufumi Katanasaka, Miho Sano, María A Zuriaga, Minoru Yoshiyama, David Goukassian, Matthew A Cooper, José J Fuster, Kenneth Walsh
BACKGROUND: Recent studies have shown that hematopoietic stem cells can undergo clonal expansion secondary to somatic mutations in leukemia-related genes, thus leading to an age-dependent accumulation of mutant leukocytes in the blood. This somatic mutation-related clonal hematopoiesis is common in healthy older individuals, but it has been associated with an increased incidence of future cardiovascular disease. The epigenetic regulator TET2 is frequently mutated in blood cells of individuals exhibiting clonal hematopoiesis...
February 27, 2018: Journal of the American College of Cardiology
Mei Chen, Jiawu Zhao, Imran H A Ali, Stephen Marry, Josy Augustine, Mohajeet Bhuckory, Aisling Lynch, Adrien Kissenpfennig, Heping Xu
The suppressor of cytokine signaling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysMCre/+ SOCS3fl/fl ). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysMCre/+ SOCS3fl/fl mice compared with that in wild-type (WT) mice...
April 2018: American Journal of Pathology
Tanja Schönfelder, Moritz Brandt, Sabine Kossmann, Tanja Knopp, Thomas Münzel, Ulrich Walter, Susanne H Karbach, Philip Wenzel
The role of leukocytes in deep vein thrombosis (DVT) resolution is incompletely understood. We determined how depletion of lysozyme positive (LysM+ ) cells and a switched-off type 1 immune response influences thrombus resolution. DVT was induced in 12-week-old male mice by inferior vena cava (IVC) stenosis. Toxin mediated depletion of myeloid cells improved thrombus resolution in mice with Cre-inducible expression of the diphtheria toxin receptor in LysM+ cells. This correlated with decreased CD45+ cells, a population shift of Gr-1+ to Gr-1- CD11b+ myelomonocytic cells (flow cytometry) and an increase in CC-chemokine ligand 2, interleukin-4 and interleukin-10 mRNA expressions...
February 14, 2018: Scientific Reports
Sang A Park, Young Ho Choe, Sung Hwan Lee, Young-Min Hyun
Sepsis is a type of severe infection that can cause organ failure and tissue damage. Although the mortality and morbidity rates associated with sepsis are extremely high, no direct treatment or organ-related mechanism has been examined in detail in real time. The liver is the key organ that manages toxins and infections in the human body. Herein, we aimed to perform intravital imaging of mouse liver after induction of endotoxemia in order to track the motility of immune cells, such as neutrophils and liver capsular macrophages (LCMs)...
February 6, 2018: Journal of Visualized Experiments: JoVE
Hamida Beghalem, Khadidja Aliliche, Ahmed Landoulsi
In legumes, LysM domains of receptors-like kinases (RLKs) mediate rhizobial NFs perception; which are required for infection and establishment of symbiosis without triggering the host immune response. In this study, we identify the LysM extracellular domain sequences of putative Sulla species Nod factor receptors (S. pallida, S. capitata and S. coronaria). The Blast search displayed high identity percentages with genes encoding LjNFR5-like of several legumes. Phylogenetic trees were built using the partial nod factor receptor and predicted amino acid sequences, which grouped Sulla in a separate clade...
April 2018: Microbial Pathogenesis
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