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https://www.readbyqxmd.com/read/28096301/phosphoinositol-3-phosphate-acts-as-a-timer-for-reactive-oxygen-species-production-in-the-phagosome
#1
Zhi Min Song, Leïla Bouchab, Elodie Hudik, Romain Le Bars, Oliver Nüsse, Sophie Dupré-Crochet
Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40(phox) by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40(phox) and p67(phox) at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28095608/esx-1-and-phthiocerol-dimycocerosates-of-mycobacterium-tuberculosis-act-in-concert-to-cause-phagosomal-rupture-and-host-cell-apoptosis
#2
Jacques Augenstreich, Ainhoa Arbues, Roxane Simeone, Evert Haanappel, Alice Wegener, Fadel Sayes, Fabien Le Chevalier, Christian Chalut, Wladimir Malaga, Christophe Guilhot, Roland Brosch, Catherine Astarie-Dequeker
Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT-6). This small protein, which is secreted by the type VII secretion system ESX-1 (T7SS/ESX-1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28095485/bordetella-parapertussis-circumvents-neutrophil-extracellular-bactericidal-mechanisms
#3
Juan Gorgojo, Emilia Scharrig, Ricardo M Gómez, Eric T Harvill, Maria Eugenia Rodríguez
B. parapertussis is a whooping cough etiological agent with the ability to evade the immune response induced by pertussis vaccines. We previously demonstrated that in the absence of opsonic antibodies B. parapertussis hampers phagocytosis by neutrophils and macrophages and, when phagocytosed, blocks intracellular killing by interfering with phagolysosomal fusion. But neutrophils can kill and/or immobilize extracellular bacteria through non-phagocytic mechanisms such as degranulation and neutrophil extracellular traps (NETs)...
2017: PloS One
https://www.readbyqxmd.com/read/28093102/proteomic-changes-in-the-ileum-of-sheep-infected-with-mycobacterium-avium-subspecies-paratuberculosis
#4
S Pisanu, T Cubeddu, S Uzzau, S Rocca, M F Addis
Johne's disease (JD) is a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). To identify the processes activated in the sheep intestine during natural MAP infection, and to provide a panel of differential host and pathogen proteins with diagnostic and prognostic potential, a differential shotgun proteomics workflow, including mass spectrometry, label-free quantisation and pathway analysis, was applied to ileal tissues of ewes with and without JD. Out of 2889 total proteins identified, 384 were differentially expressed and 341 were expressed at a higher level in JD...
January 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28091553/shifts-in-the-fluorescence-lifetime-of-egfp-during-bacterial-phagocytosis-measured-by-phase-sensitive-flow-cytometry
#5
Wenyan Li, Kevin D Houston, Jessica P Houston
Phase-sensitive flow cytometry (PSFC) is a technique in which fluorescence excited state decay times are measured as fluorescently labeled cells rapidly transit a finely focused, frequency-modulated laser beam. With PSFC the fluorescence lifetime is taken as a cytometric parameter to differentiate intracellular events that are challenging to distinguish with standard flow cytometry. For example PSFC can report changes in protein conformation, expression, interactions, and movement, as well as differences in intracellular microenvironments...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28081295/connected-component-masking-accurately-identifies-the-ratio-of-phagocytosed-and-cell-bound-particles-in-individual-cells-by-imaging-flow-cytometry
#6
Chenjie Fei, Dustin M E Lillico, Brian Hall, Aja M Rieger, James L Stafford
Innate immune cell-mediated recognition, capture, and engulfment of large particulate targets such as bacteria is known as phagocytosis. This highly dynamic cellular process involves a series of steps including receptor-mediated target binding, phagocytic cup formation, pseudopod extension, and phagosome closure, which depend on distinct actin polymerization events. Using flow cytometry, precise determination of target locations relative to cell membranes (i.e., surface-bound vs. fully engulfed/internalized) during the phagocytic process is difficult to quantify...
January 12, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28079153/nf-%C3%AE%C2%BAb-activation-is-critical-for-bacterial-lipoprotein-tolerance-enhanced-bactericidal-activity-in-macrophages-during-microbial-infection
#7
Jinghua Liu, Jing Xiang, Xue Li, Siobhan Blankson, Shuqi Zhao, Junwei Cai, Yong Jiang, H Paul Redmond, Jiang Huai Wang
Tolerance to bacterial components represents an essential regulatory mechanism during bacterial infection. Bacterial lipoprotein (BLP)-induced tolerance confers protection against microbial sepsis by attenuating inflammatory responses and augmenting antimicrobial activity in innate phagocytes. It has been well-documented that BLP tolerance-attenuated proinflammatory cytokine production is associated with suppressed TLR2 signalling pathway; however, the underlying mechanism(s) involved in BLP tolerance-enhanced antimicrobial activity is unclear...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063015/innate-immunity-against-legionella-pneumophila-during-pulmonary-infections-in-mice
#8
REVIEW
Bonggoo Park, Gayoung Park, Jiyoung Kim, Seon Ah Lim, Kyung-Mi Lee
Legionella pneumophila is an etiological agent of the severe pneumonia known as Legionnaires' disease (LD). This gram-negative bacterium is thought to replicate naturally in various freshwater amoebae, but also replicates in human alveolar macrophages. Inside host cells, legionella induce the production of non-endosomal replicative phagosomes by injecting effector proteins into the cytosol. Innate immune responses are first line defenses against legionella during early phases of infection, and distinguish between legionella and host cells using germline-encoded pattern recognition receptors such as Toll-like receptors , NOD-like receptors, and RIG-I-like receptors, which sense pathogen-associated molecular patterns that are absent in host cells...
January 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28057704/mycobacterium-tuberculosis-protease-marp-activates-a-peptidoglycan-hydrolase-during-acid%C3%A2-stress
#9
Helene Botella, Julien Vaubourgeix, Myung Hee Lee, Naomi Song, Weizhen Xu, Hideki Makinoshima, Michael S Glickman, Sabine Ehrt
Mycobacterium tuberculosis (Mtb) can persist in the human host in a latent state for decades, in part because it has the ability to withstand numerous stresses imposed by host immunity. Prior studies have established the essentiality of the periplasmic protease MarP for Mtb to survive in acidified phagosomes and establish and maintain infection in mice. However, the proteolytic substrates of MarP that mediate these phenotypes were unknown. Here, we used biochemical methods coupled with supravital chemical probes that facilitate imaging of nascent peptidoglycan to demonstrate that during acid stress MarP cleaves the peptidoglycan hydrolase RipA, a process required for RipA's activation...
January 5, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28050854/saxifragifolin-d-attenuates-phagosome-maturation-arrest-in-mycobacterium-tuberculosis-infected-macrophages-via-an-ampk-and-vps34-dependent-pathway
#10
Jia Zhou, Rui Xu, Xian-Zhi Du, Xiang-Dong Zhou, Qi Li
Saxifragifolin D (SD), a traditional Chinese medicine, is a pentacyclic triterpenoid compound first isolated from Androsace umbellata. Various plant triterpenoids have been reported to exhibit antitubercular activity. In this study, THP-1-derived macrophages were infected with an attenuated M. tuberculosis (M.tb) strain, H37Ra. Intracellular replication of M.tb was evaluated by counting the colonies after 4 weeks of incubation. The results indicated that SD treatment reduced the intracellular replication of M...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28045572/rna-seq-unveils-new-attributes-of-the-heterogeneous-salmonella-host-cell-communication
#11
Francisco García-Del Portillo, M Graciela Pucciarelli
High-throughput RNA sequencing (RNA-Seq) has uncovered hundreds of small RNAs and complex modes of RNA regulation in every bacterium analyzed to date. This complexity agrees with the adaptability of most bacteria to varied environments including, in the case of pathogens, the new niches encountered in the host. Recent RNA-Seq studies have analyzed simultaneously gene expression in the intracellular pathogen Salmonella enterica and infected host cells at population and single-cell level. Distinct polarization states or interferon responses in the infected macrophage were linked to variable growth rates or activities of defined virulence regulators in intra-phagosomal bacteria...
January 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/28036233/shared-and-distinct-aspects-of-the-sepsis-transcriptomic-response-to-fecal-peritonitis-and-pneumonia
#12
Katie L Burnham, Emma E Davenport, Jayachandran Radhakrishnan, Peter Humburg, Anthony C Gordon, Paula Hutton, Eduardo Svoren-Jabalera, Christopher Garrard, Adrian Vs Hill, Charles J Hinds, Julian C Knight
RATIONALE: Heterogeneity in the septic response has hindered efforts to understand pathophysiology and develop targeted therapies. Source of infection, with different causative organisms and temporal changes, might influence this heterogeneity. OBJECTIVES: To investigate individual and temporal variation in the transcriptomic response to sepsis due to fecal peritonitis, and to compare with community acquired pneumonia. METHODS: We performed genome-wide gene expression profiling in peripheral blood leukocytes for adult patients admitted to intensive care with sepsis due to fecal peritonitis (n=117) or community acquired pneumonia (n=126), and non-septic controls (n=10)...
December 30, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28035045/multiphasic-dynamics-of-phosphatidylinositol-4-phosphate-during-phagocytosis
#13
Roni Levin, Gerald R V Hammond, Tamas Balla, Pietro De Camilli, Gregory D Fairn, Sergio Grinstein
We analyzed the distribution, fate, and functional role of phosphatidylinositol 4-phosphate (PtdIns4P) during phagosome formation and maturation. To this end, we used genetically encoded probes consisting of the PtdIns4P-binding domain of the bacterial effector SidM. PtdIns4P was found to undergo complex, multiphasic changes during phagocytosis. The phosphoinositide, which is present in the plasmalemma before engagement of the target particle, is transiently enriched in the phagosomal cup. Soon after the phagosome seals, PtdIns4P levels drop precipitously due to the hydrolytic activity of Sac2 and phospholipase C, becoming undetectable for ∼10 min...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28031264/mycobacterium-bovis-requires-p27-lprg-to-arrest-phagosome-maturation-and-replicate-within-bovine-macrophages
#14
Cristina Lourdes Vázquez, María Verónica Bianco, Federico Carlos Blanco, Marina Forrellad, Maximiliano Gabriel Gutierrez, Fabiana Bigi
Mycobacterium bovis causes tuberculosis in a wide variety of mammals with strong tropism for cattle and eventually humans. P27, also called LprG, is among the proteins involved in the mechanisms of virulence and persistence of M. bovis and Mycobacterium tuberculosis Here, we describe a novel function of P27 in the interaction of M. bovis with its natural host cell, the bovine macrophage. We found that a deletion in the p27-p55 operon impairs the replication of M. bovis in bovine macrophages. Importantly, we show for the first time that M...
December 28, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/28026004/ethanol-enhances-thymocyte-apoptosis-and-autophagy-in-macrophages-of-rat-thymi
#15
Tsubasa Betsuyaku, Nabil Eid, Yuko Ito, Yoshihisa Tanaka, Yoshinori Otsuki, Yoichi Kondo
Tingible body macrophages (TBMs) play essential roles in the phagocytosis of apoptotic lymphocytes, specifically under exposure to various stressors. Although excessive ethanol consumption may enhance thymocyte apoptosis, reports investigating the autophagic response of the thymus to ethanol toxicity are still lacking. We investigated apoptosis and autophagy in thymi of an animal model of binge ethanol exposure. Adult male Wistar rats were injected intraperitoneally either with 5 g/kg ethanol or phosphate buffer saline (for the control group) and sacrificed 0, 3, 6 and 24 hours after injection...
December 27, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/28012988/the-host-immune-enhancing-agent-korean-red-ginseng-oil-successfully-attenuates-brucella-abortus-infection-in-a-murine-model
#16
Alisha Wehdnesday Bernardo Reyes, Huynh Tan Hop, Lauren Togonon Arayan, Tran Xuan Ngoc Huy, Soo Jong Park, Kwang Dong Kim, WonGi Min, Hu Jang Lee, Man Hee Rhee, Yi-Seong Kwak, Suk Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng Meyer (Araliaceae), is one of the most valuable traditional Chinese medicines and is used for the treatment of various human diseases. In this study, we elucidated the protective mechanism of the essential oil from Korean red ginseng (RGO) against Brucella infection. MATERIALS AND METHODS: The effects of RGO on Brucella abortus viability, NO production, uptake and intracellular growth in macrophages were investigated...
December 21, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28011901/efferocytosis-is-impaired-in-gaucher-macrophages
#17
Elma Aflaki, Daniel K Borger, Richard J Grey, Martha Kirby, Stacie Anderson, Grisel Lopez, Ellen Sidransky
Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67phox and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes...
December 23, 2016: Haematologica
https://www.readbyqxmd.com/read/28008422/pathogenic-mycobacteria-achieve-cellular-persistence-by-inhibiting-the-niemann-pick-type-c-disease-cellular-pathway
#18
Paul Fineran, Emyr Lloyd-Evans, Nathan A Lack, Nick Platt, Lianne C Davis, Anthony J Morgan, Doris Höglinger, Raju Venkata V Tatituri, Simon Clark, Ian M Williams, Patricia Tynan, Nada Al Eisa, Evgeniya Nazarova, Ann Williams, Antony Galione, Daniel S Ory, Gurdyal S Besra, David G Russell, Michael B Brenner, Edith Sim, Frances M Platt
BACKGROUND: Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death...
November 18, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28005073/rab17-mediates-differential-antigen-sorting-following-efferocytosis-and-phagocytosis
#19
Charles Yin, Yohan Kim, Dean Argintaru, Bryan Heit
Macrophages engulf and destroy pathogens (phagocytosis) and apoptotic cells (efferocytosis), and can subsequently initiate adaptive immune responses by presenting antigens derived from engulfed materials. Both phagocytosis and efferocytosis share a common degradative pathway in which the target is engulfed into a membrane-bound vesicle, respectively, termed the phagosome and efferosome, where they are degraded by sequential fusion with endosomes and lysosomes. Despite this shared maturation pathway, macrophages are immunogenic following phagocytosis but not efferocytosis, indicating that differential processing or trafficking of antigens must occur...
December 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/28000679/mycobacterium-tuberculosis-cell-wall-released-fragments-by-the-action-of-the-human-lung-mucosa-modulate-macrophages-to-control-infection-in-an-il-10-dependent-manner
#20
J Arcos, S J Sasindran, J I Moliva, J M Scordo, S Sidiki, H Guo, P Venigalla, H V Kelley, G Lin, L Diangelo, S N Silwani, J Zhang, J Turner, J B Torrelles
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is a major public health challenge facing the world. During infection, M.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (ALF), an environment that M.tb encounters at different stages of the infection and disease. ALF is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. Here we demonstrate that ALF hydrolases, at their physiological concentrations and upon contact with M...
December 21, 2016: Mucosal Immunology
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