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Phagosome

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https://www.readbyqxmd.com/read/28448042/imaging-the-neutrophil-phagosome-and-cytoplasm-using-a-ratiometric-ph-indicator
#1
Juliet R Foote, Adam P Levine, Philippe Behe, Michael R Duchen, Anthony W Segal
Neutrophils are crucial to host innate defense and, consequently, constitute an important area of medical research. The phagosome, the intracellular compartment where the killing and digestion of engulfed particles take place, is the main arena for neutrophil pathogen killing that requires tight regulation. Phagosomal pH is one aspect that is carefully controlled, in turn regulating antimicrobial protease activity. Many fluorescent pH-sensitive dyes have been used to visualize the phagosomal environment. S-1 has several advantages over other pH-sensitive dyes, including its dual emission spectra, its resistance to photo-bleaching, and its high pKa...
April 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28438978/peptoanaerobacter-stomatis-primes-human-neutrophils-and-induces-granule-exocytosis
#2
E Jimenez Flores, S Tian, M Sizova, S S Epstein, R J Lamont, S M Uriarte
Peptoanaerobacter stomatis is a newly appreciated taxon associated with periodontal diseases; however, little is known about the organism's pathogenic potential or its interaction with the host immune response. Neutrophils are the most abundant innate immune cell present in the gingival tissue and function to constrain the oral microbial challenge. However, some periodontal pathogens have developed strategies to evade phagocytosis and killing by neutrophils. Therefore, to begin to understand the role of P. stomatis in periodontitis, we studied its interactions with human neutrophils...
April 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28436493/an-attenuated-mycobacterium-tuberculosis-clinical-strain-with-a-defect-in-esx-1-secretion-induces-minimal-host-immune-responses-and-pathology
#3
Helena Strand Clemmensen, Niels Peter Hell Knudsen, Erik Michael Rasmussen, Jessica Winkler, Ida Rosenkrands, Ahmad Ahmad, Troels Lillebaek, David R Sherman, Peter Lawætz Andersen, Claus Aagaard
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432021/the-er-phagosome-connection-in-the-era-of-membrane-contact-sites
#4
REVIEW
Paula Nunes-Hasler, Nicolas Demaurex
Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28428627/glucocorticoids-suppress-antimicrobial-autophagy-and-nitric-oxide-production-and-facilitate-mycobacterial-survival-in-macrophages
#5
Jinli Wang, Ruining Wang, Hui Wang, Xiaofan Yang, Jiahui Yang, Wenjing Xiong, Qian Wen, Li Ma
Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424218/gop-1-promotes-apoptotic-cell-degradation-by-activating-the-small-gtpase-rab2-in-c-elegans
#6
Jianhua Yin, Yaling Huang, Pengfei Guo, Siqi Hu, Sawako Yoshina, Nan Xuan, Qiwen Gan, Shohei Mitani, Chonglin Yang, Xiaochen Wang
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified gop-1 as a novel regulator of apoptotic cell clearance in Caenorhabditis elegans Loss of gop-1 affects phagosome maturation through the RAB-5-positive stage, causing defects in phagosome acidification and phagolysosome formation, phenotypes identical to and unaffected by loss of unc-108, the C...
April 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28416446/patterns-receptors-and-signals-regulation-of-phagosome-maturation
#7
REVIEW
Anne-Marie Pauwels, Matthias Trost, Rudi Beyaert, Eik Hoffmann
Recognition of microbial pathogens and dead cells and their phagocytic uptake by specialized immune cells are essential to maintain host homeostasis. Phagosomes undergo fusion and fission events with endosomal and lysosomal compartments, a process called 'phagosome maturation', which leads to the degradation of the phagosomal content. However, many phagocytic cells also act as antigen-presenting cells and must balance degradation and peptide preservation. Emerging evidence indicates that receptor engagement by phagosomal cargo, as well as inflammatory mediators and cellular activation affect many aspects of phagosome maturation...
April 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28412201/nitric-oxide-enhanced-the-growth-of-an-obligated-intracellular-bacterium-orientia-tsutsugamushi-in-murine-macrophages
#8
Motohiko Ogawa, Masaaki Satoh, Michiyo Kataoka, Shuji Ando, Masayuki Saijo
Orientia tsutsugamushi is the causative agent of scrub typhus. It is an obligate intracellular bacterium that grows only in eukaryotic cells. Macrophages play an important role in innate immunity by surveilling the human body for pathogens. In present study, it was demonstrated that O. tsutsugamushi propagated well in LPS-activated RAW 264.7 macrophages, but not in non-activated macrophages. In LPS-activated macrophages, the expression of Nos2, which encodes the inducible nitric oxide (NO) synthase (iNOS), was highly upregulated compared to those in non-activated macrophages...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28410133/the-role-of-lipids-in-host-microbe-interactions
#9
Roland Lang, Jochen Mattner
Lipids are one of the major subcellular constituents and serve as signal molecules, energy sources, metabolic precursors and structural membrane components in various organisms. The function of lipids can be modified by multiple biochemical processes such as (de-)phosphorylation or (de-)glycosylation, and the organization of fatty acids into distinct cellular pools and subcellular compartments plays a pivotal role for the morphology and function of various cell populations. Thus, lipids regulate, for example, phagosome formation and maturation within host cells and thus, are critical for the elimination of microbial pathogens...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28409542/inhibitory-receptor-fc%C3%AE-riib-mediates-the-effects-of-igg-on-a-phagosome-acidification-and-a-sequential-dephosphorylation-system-comprising-ships-and-inpp4a
#10
Tomohiro Segawa, Kaoru Hazeki, Kiyomi Nigorikawa, Atsuko Nukuda, Tomoki Tanizawa, Kenshiro Miyamoto, Shin Morioka, Osamu Hazeki
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in the forming of the phagocytic cup, following which they disappear after sealing of the cup. In the present study, we monitored the clearance of these PI species using the enhanced green fluorescent protein-fused pleckstrin homology domain of Akt, a fluorescence probe that binds both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28401066/importance-of-metabolic-adaptations-in-francisella-pathogenesis
#11
REVIEW
Jason Ziveri, Monique Barel, Alain Charbit
Francisella tularensis is a highly infectious Gram-negative bacterium and the causative agent of the zoonotic disease tularemia. This bacterial pathogen can infect a broad variety of animal species and can be transmitted to humans in numerous ways with various clinical outcomes. Although, Francisella possesses the capacity to infect numerous mammalian cell types, the macrophage constitutes the main intracellular niche, used for in vivo bacterial dissemination. To survive and multiply within infected macrophages, Francisella must imperatively escape from the phagosomal compartment...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28393860/mycobacterium-llatzerense-a-waterborne-mycobacterium-that-resists-phagocytosis-by-acanthamoeba-castellanii
#12
Vincent Delafont, Ascel Samba-Louaka, Emmanuelle Cambau, Didier Bouchon, Laurent Moulin, Yann Héchard
Nontuberculous mycobacteria (NTM) are environmental bacteria increasingly associated to public health problems. In water systems, free-living amoebae (FLA) feed on bacteria by phagocytosis, but several bacteria, including many NTM, are resistant to this predation. Thus, FLA can be seen as a training ground for pathogenic bacteria. Mycobacterium llatzerense was previously described as frequently associated with FLA in a drinking water network. The present study aimed to characterize the interactions between M...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28390980/semi-synthetic-sapogenin-exerts-neuroprotective-effects-by-skewing-the-brain-ischemia-reperfusion-transcriptome-towards-inflammatory-resolution
#13
Laura García-Pupo, Jeney Ramírez Sánchez, Dariusz Ratman, Claudina Pérez-Novo, Ken Declerck, Karolien De Bosscher, Marios Nektarios Markakis, Gerrit Beemster, Armando Zaldo, Yanier Nuñez Figueredo, René Delgado Hernández, Wim Vanden Berghe
Stroke represents one of the first causes of mortality and morbidity worldwide. We evaluated the therapeutic potential of a novel semi-synthetic spirosteroid sapogenin derivative "S15" in a transient middle cerebral artery occlusion (tMCAO) focal ischemia model in rat. S15-treated rats had significantly reduced infarct volumes and improved neurological functions at 24 h post-reperfusion, compared with ischemia. Corresponding gene expression changes in brain were characterized by mRNA sequencing and qPCR approaches...
April 5, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28384255/trehalose-dimycolate-interferes-with-fc%C3%AE-r-mediated-phagosome-maturation-through-mincle-shp-1-and-fc%C3%AE-riib-signalling
#14
Emmanuel C Patin, Anna C Geffken, Sam Willcocks, Christoph Leschczyk, Albert Haas, Falk Nimmerjahn, Roland Lang, Theresa H Ward, Ulrich E Schaible
The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6'-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes survival of mycobacteria inside host macrophages by a not fully understood mechanism. TDM signals through the Monocyte-INducible C-type LEctin (Mincle), a recently identified pattern recognition receptor. Here we show that recruitment of Mincle by TDM coupled to immunoglobulin (Ig)G-opsonised beads during Fcγ receptor (FcγR)-mediated phagocytosis interferes with phagosome maturation...
2017: PloS One
https://www.readbyqxmd.com/read/28377926/platinum-based-drugs-differentially-affect-the-ultrastructure-of-breast-cancer-cell-types
#15
Shadia Al-Bahlani, Buthaina Al-Dhahli, Kawther Al-Adawi, Abdurahman Al-Nabhani, Mohamed Al-Kindi
Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28377902/role-of-glycosylation-deglycolysation-processes-in-francisella-tularensis-pathogenesis
#16
REVIEW
Monique Barel, Alain Charbit
Francisella tularensis is able to invade, survive and replicate inside a variety of cell types. However, in vivo F. tularensis preferentially enters host macrophages where it rapidly escapes to the cytosol to avoid phagosomal stresses and to multiply to high numbers. We previously showed that human monocyte infection by F. tularensis LVS triggered deglycosylation of the glutamine transporter SLC1A5. However, this deglycosylation, specifically induced by Francisella infection, was not restricted to SLC1A5, suggesting that host protein deglycosylation processes in general might contribute to intracellular bacterial adaptation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28376111/coordinated-balance-of-rac1-and-rhoa-plays-key-roles-in-determining-phagocytic-appetite
#17
Sang-Yeob Kim, Soyoun Kim, Dong-Jun Bae, Seung-Yoon Park, Ga-Young Lee, Gyeong-Min Park, In-San Kim
The removal of unwanted or damaged cells by phagocytes is achieved via a finely regulated cleaning process called efferocytosis. To characterize the mechanisms through which phagocytes control the intake of apoptotic cells, we investigated how the phagocyte's appetite for engulfed cells may be coordinated by RhoA and Rac1 in the phagocytic cup. We used FRET biosensors to visualize the spatiotemporal dynamics of Rho-family GTPases, and found that RhoA, which is known to be downregulated during phagocytosis, was transiently upregulated at the phagocytic cup immediately prior to ingestion...
2017: PloS One
https://www.readbyqxmd.com/read/28368693/galectins-and-trims-directly-interact-and-orchestrate-autophagic-response-to-endomembrane-damage
#18
Suresh Kumar, Santosh Chauhan, Ashish Jain, Marisa Ponpuak, Seong Won Choi, Michal Mudd, Ryan Peters, Michael A Mandell, Terje Johansen, Vojo Deretic
Macroautophagy/autophagy is a homeostatic process delivering cytoplasmic targets, including damaged organelles, to lysosomes for degradation; however, it is not completely understood how compromised endomembranes are recognized by the autophagic apparatus. We have described previously that the TRIM family of proteins act as receptors for selective autophagy. In this study we uncovered the property of TRIMs to directly interact with members of the family of cytosolic lectins termed galectins. Galectins patrol the cytoplasm and recognize compromised membranes...
April 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28357032/meta-analysis-reveals-up-regulation-of-cholesterol-processes-in-non-alcoholic-and-down-regulation-in-alcoholic-fatty-liver-disease
#19
Wasco Wruck, James Adjaye
AIM: To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies. METHODS: Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD. RESULTS: We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome...
March 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28345623/liposomes-loaded-with-bioactive-lipids-enhance-antibacterial-innate-immunity-irrespective-of-drug-resistance
#20
Noemi Poerio, Francesca Bugli, Francesco Taus, Marilina B Santucci, Carlo Rodolfo, Francesco Cecconi, Riccardo Torelli, Francesco Varone, Riccardo Inchingolo, Fabio Majo, Vincenzina Lucidi, Sabrina Mariotti, Roberto Nisini, Maurizio Sanguinetti, Maurizio Fraziano
Phagocytosis is a key mechanism of innate immunity, and promotion of phagosome maturation may represent a therapeutic target to enhance antibacterial host response. Phagosome maturation is favored by the timely and coordinated intervention of lipids and may be altered in infections. Here we used apoptotic body-like liposomes (ABL) to selectively deliver bioactive lipids to innate cells, and then tested their function in models of pathogen-inhibited and host-impaired phagosome maturation. Stimulation of macrophages with ABLs carrying phosphatidic acid (PA), phosphatidylinositol 3-phosphate (PI3P) or PI5P increased intracellular killing of BCG, by inducing phagosome acidification and ROS generation...
March 27, 2017: Scientific Reports
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