'Phagocytosis is central to bacterial clearance, but the exact mechanism is incompletely understood. Here, we show a novel and critical role for lumican, the connective tissue extracellular matrix small leucine-rich repeat proteoglycan, in CD14-mediated bacterial phagocytosis. In Psuedomonas aeruginosa lung infections, lumican-deficient (Lum(-/-)) mice failed to clear the bacterium from ... More
SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages.
AuthorsBerger SB, Romero X, Ma C, Wang G, Faubion WA, Liao G, Compeer E, Keszei M, Rameh L, Wang N, Boes M, Regueiro JR, Reinecker HC, Terhorst C,
JournalNat Immunol
PubMed ID20818396
'Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of gram-negative bacteria by macrophages. ... More
Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin.
AuthorsFiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J
JournalProc Natl Acad Sci U S A
PubMed ID17652175
'We have tested a hypothesis that the natural product curcuminoids, which has epidemiologic and experimental rationale for use in AD, may improve the innate immune system and increase amyloid-beta (Abeta) clearance from the brain of patients with sporadic Alzheimer''s disease (AD). Macrophages of a majority of AD patients do not ... More
Establishment of single-cell screening system for the rapid identification of transcriptional modulators involved in direct cell reprogramming.
AuthorsShin JW, Suzuki T, Ninomiya N, Kishima M, Hasegawa Y, Kubosaki A, Yabukami H, Hayashizaki Y, Suzuki H,
JournalNucleic Acids Res
PubMed ID22879381
'Combinatorial interactions of transcription modulators are critical to regulate cell-specific expression and to drive direct cell reprogramming (e.g. trans-differentiation). However, the identification of key transcription modulators from myriad of candidate genes is laborious and time consuming. To rapidly identify key regulatory factors involved in direct cell reprogramming, we established a ... More
Rooperol as an antioxidant and its role in the innate immune system: An in vitro study.
AuthorsBoukes GJ, van de Venter M,
JournalJ Ethnopharmacol
PubMed ID23085395
'Biologically active rooperol is formed when the glucose subunits of the nontoxic glycoside, hypoxoside, are cleaved by ß-glucosidase. Hypoxoside is isolated from Hypoxis, a medicinal plant genus frequently used by the indigenous people of South Africa as an immune system booster. The aim of this study was to investigate rooperol''s ... More
Disease-causing mutations in the cystic fibrosis transmembrane conductance regulator determine the functional responses of alveolar macrophages.
'Alveolar macrophages (AMs) play a major role in host defense against microbial infections in the lung. To perform this function, these cells must ingest and destroy pathogens, generally in phagosomes, as well as secrete a number of products that signal other immune cells to respond. Recently, we demonstrated that murine ... More
A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction.
AuthorsZemans RL, Briones N, Young SK, Malcolm KC, Refaeli Y, Downey GP, Worthen GS,
JournalJ Immunol Methods
PubMed ID19010330
'Neutrophils are a critical component of the innate immune response to invading microbial pathogens. However, an excessive and/or prolonged neutrophil response can result in tissue injury that is thought to underlie the pathogenesis of various inflammatory diseases. The development of novel therapeutic strategies for inflammatory diseases depends on an improved ... More
Glucose-6-phosphatase-ß, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality.
AuthorsJun HS, Cheung YY, Lee YM, Mansfield BC, Chou JY,
JournalBlood
PubMed ID22246029
'Glucose-6-phosphatase-ß (G6Pase-ß or G6PC3) deficiency, also known as severe congenital neutropenia syndrome 4, is characterized not only by neutropenia but also impaired neutrophil energy homeostasis and functionality. We now show the syndrome is also associated with macrophage dysfunction, with murine G6pc3(-/-) macrophages having impairments in their respiratory burst, chemotaxis, calcium ... More
Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients.
'BACKGROUND: Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and ... More
VIP36 protein is a target of ectodomain shedding and regulates phagocytosis in macrophage Raw 264.7 cells.
AuthorsShirakabe K, Hattori S, Seiki M, Koyasu S, Okada Y,
JournalJ Biol Chem
PubMed ID22016386
'Ectodomain shedding is a posttranslational modification mechanism, which liberates extracellular domains of membrane proteins through juxtamembrane processing executed mainly by the ADAM (a disintegrin and metalloprotease) family of metalloproteases. Shedding is a unique and effective mechanism for inducing multifaceted effects through the soluble extracellular domains released and/or the remaining membrane-bound ... More
Antibody-Dependent, Fc?RI-Mediated Neutralization of HIV-1 in TZM-bl Cells Occurs Independently of Phagocytosis.
AuthorsPerez LG, Zolla-Pazner S, Montefiori DC,
JournalJ Virol
PubMed ID23408628
'We previously showed that expression of human Fc?RI on TZM-bl cells potentiates neutralization by gp41 membrane-proximal external region (MPER)-specific antibodies. Here we show that lysosomotropic reagents known to block phagocytosis do not diminish this effect. We also show that Fc?RI occasionally potentiates neutralization by antibodies against the V3 loop of ... More
Imaging microglia in brain slices and slice cultures.
AuthorsDailey ME, Eyo U, Fuller L, Hass J, Kurpius D,
Journal
PubMed ID24298036
Here we describe a method for imaging fluorescently labeled parenchymal microglia (MG) in excised neonatal or adult rodent brain tissue slices. Using multichannel confocal or two-photon time-lapse imaging, the approach affords real-time analyses of MG behaviors, including motility, migration, chemotaxis, proliferation, and phagocytosis in live brain tissues. The method is ... More
Functional analysis of a zebrafish myd88 mutant identifies key transcriptional components of the innate immune system.
Authorsvan der Vaart M, van Soest JJ, Spaink HP, Meijer AH,
JournalDis Model Mech
PubMed ID23471913
Toll-like receptors (TLRs) are an important class of pattern recognition receptors (PRRs) that recognize microbial and danger signals. Their downstream signaling upon ligand binding is vital for initiation of the innate immune response. In human and mammalian models, myeloid differentiation factor 88 (MYD88) is known for its central role as ... More
Activation of the liver X receptor-ß potently inhibits osteoclastogenesis from lipopolysaccharide-exposed bone marrow-derived macrophages.
AuthorsRobertson Remen KM, Lerner UH, Gustafsson JÅ, Andersson G,
JournalJ Leukoc Biol
PubMed ID23099324
Bacterial-induced bone diseases, such as periodontitis and osteomyelitis, are chronic inflammatory diseases characterized by increased bone destruction as a result of enhanced osteoclastogenesis. The LXRa and -ß are important modulators of inflammatory signaling and can potently inhibit RANKL-induced osteoclast differentiation. Here, we investigated the effects of the LXR agonist GW3965 ... More
Pivotal advance: peritoneal cavity B-1 B cells have phagocytic and microbicidal capacities and present phagocytosed antigen to CD4+ T cells.
AuthorsParra D, Rieger AM, Li J, Zhang YA, Randall LM, Hunter CA, Barreda DR, Sunyer JO,
JournalJ Leukoc Biol
PubMed ID22058420
Breaking the long-held paradigm that primary B cells are not phagocytic, several studies have demonstrated recently that B cells from fish, amphibians, and reptilians have a significant phagocytic capacity. Whether such capacity has remained conserved in certain mammalian B cell subsets is presently an enigma. Here, we report a previously ... More
Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance.
AuthorsUlvila J, Vanha-aho LM, Kleino A, Vähä-Mäkilä M, Vuoksio M, Eskelinen S, Hultmark D, Kocks C, Hallman M, Parikka M, Rämet M,
JournalJ Leukoc Biol
PubMed ID21208897
Phagocytosis is an ancient cellular process that plays an important role in host defense. In Drosophila melanogaster phagocytic, macrophage-like hemocytes recognize and ingest microbes. We performed an RNAi-based in vitro screen in the Drosophila hemocyte cell line S2 and identified Abi, cpa, cofilin regulator 14-3-3?, tlk, CG2765, and CG15609 as ... More
HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy.
AuthorsHearps AC, Maisa A, Cheng WJ, Angelovich TA, Lichtfuss GF, Palmer CS, Landay AL, Jaworowski A, Crowe SM,
JournalAIDS
PubMed ID22313961
OBJECTIVES:: To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals. DESIGN:: A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV-positive males aged 45 years or ... More
Characterization of the mononuclear phagocyte system in zebrafish.
The evolutionarily conserved immune system of the zebrafish (Danio rerio), in combination with its genetic tractability, position it as an excellent model system in which to elucidate the origin and function of vertebrate immune cells. We recently reported the existence of antigen-presenting mononuclear phagocytes in zebrafish, namely macrophages and dendritic ... More
Development and validation of a flow cytometric method to evaluate phagocytosis of pHrodo™ BioParticles® by granulocytes in multiple species.
AuthorsNeaga A, Lefor J, Lich KE, Liparoto SF, Xiao YQ,
JournalJ Immunol Methods
PubMed ID21767540
Phagocytosis plays a pivotal and essential role in host immune defense, both as a focal constituent of the innate immune response and a bridging element linking innate and adaptive immunity. Phagocytosis has been demonstrated to be critical in development, tissue remodeling, wound healing and resolution of inflammation through clearance of ... More
Molecular identification of a SNAP-25-like SNARE protein in Paramecium.
Using database searches of the completed Paramecium tetraurelia macronuclear genome with the metazoan SNAP-25 homologues, we identified a single 21-kDa Qb/c-SNARE in this ciliated protozoan, named P. tetraurelia SNAP (PtSNAP), containing the characteristic dual heptad repeat SNARE motifs of SNAP-25. The presence of only a single Qb/c class SNARE in ... More
Contribution of membrane trafficking perturbation to retinal toxicity.
AuthorsKhoh-Reiter S, Sokolowski SA, Jessen B, Evans M, Dalvie D, Lu S,
Journal
PubMed ID25771199
The retina is a highly structured tissue that is formed by layers containing 7 different cell types. The photoreceptor cell is a specialized type of neuron in the retina that is capable of absorbing and converting light into electrophysiological signals. There is a constant renewal process for photoreceptors consisting of ... More
Live cell imaging of zebrafish leukocytes.
AuthorsHall C, Flores MV, Crosier K, Crosier P,
JournalMethods Mol Biol
PubMed ID19378109
Zebrafish are ideally suited for the live imaging of early immune cell compartments. Macrophages that initially appear on the yolk surface prior to the onset of circulation are the first functional immune cells within the embryo, predating the emergence of the first granulocytic cells-the heterophilic neutrophils. Both cell types have ... More
Glutathione reductase facilitates host defense by sustaining phagocytic oxidative burst and promoting the development of neutrophil extracellular traps.
AuthorsYan J, Meng X, Wancket LM, Lintner K, Nelin LD, Chen B, Francis KP, Smith CV, Rogers LK, Liu Y,
JournalJ Immunol
PubMed ID22279102
Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, which plays an important role in the bactericidal function of phagocytes. Because Gsr has been implicated in the oxidative burst in human neutrophils and is abundantly expressed in the lymphoid system, we hypothesized that Gsr-deficient mice would exhibit marked ... More
Surfactant protein-A and toll-like receptor-4 modulate immune functions of preterm baboon lung dendritic cell precursor cells.
AuthorsAwasthi S, Madhusoodhanan R, Wolf R,
JournalCell Immunol
PubMed ID21439559
Lung infections are important risk factors for an increased morbidity and mortality in prematurely-delivered babies. Immaturity of the innate immune components makes them extremely susceptible to infection. Recently, we isolated lung dendritic cell (DC)-precursor cells from preterm fetal baboons. The isolated cells were found to be defective in phagocytosing Escherichia ... More
The activation of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells.
AuthorsTakenouchi T, Nakai M, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Wei J, Sekigawa A, Sato M, Kojima S, Kitani H, Hashimoto M,
JournalJ Immunol
PubMed ID19201858
Recently, autophagy has been associated with the TLR signaling pathway to eliminate intracellular pathogens in the innate immune system. However, it is unknown if other pathways regulate autophagy during the immunologic response. Given the critical role of the purinergic P2X7 receptor (P2X7R) pathway during various immunologic functions (i.e., caspase activation ... More
Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing.
Authors
JournalNat Commun
PubMed ID35752626
Transcriptional signature in microglia associated with Aβ plaque phagocytosis.
Authors
JournalNat Commun
PubMed ID34021136
Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells.
Authors
JournalTheranostics
PubMed ID31903134
Microglial identity and inflammatory responses are controlled by the combined effects of neurons and astrocytes.
Authors
JournalCell Rep
PubMed ID33761343
Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes.
Authors
JournalDiabetologia
PubMed ID31511930
Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection.
Authors
JournalScience
PubMed ID30923196
Systematic Identification of Host Cell Regulators of Legionella pneumophila Pathogenesis Using a Genome-wide CRISPR Screen.
Authors
JournalCell Host Microbe
PubMed ID31540829
PIP2 depletion and altered endocytosis caused by expression of Alzheimer's disease-protective variant PLCγ2 R522.
Authors
JournalEMBO J
PubMed ID34254352
Macrophages Use Distinct Actin Regulators to Switch Engulfment Strategies and Ensure Phagocytic Plasticity In Vivo.