Read by QxMD icon Read


Piya Ghose, Alina Rashid, Peter Insley, Meera Trivedi, Pavak Shah, Anupriya Singhal, Yun Lu, Zhirong Bao, Shai Shaham
Phagocytosis of dying cells is critical in development and immunity1-3 . Although proteins for recognition and engulfment of cellular debris following cell death are known4,5 , proteins that directly mediate phagosome sealing are uncharacterized. Furthermore, whether all phagocytic targets are cleared using the same machinery is unclear. Degeneration of morphologically complex cells, such as neurons, glia and melanocytes, produces phagocytic targets of various shapes and sizes located in different microenvironments6,7 ...
March 19, 2018: Nature Cell Biology
Michelle E Maxson, Xenia Naj, Teresa R O'Meara, Jonathan D Plumb, Leah E Cowen, Sergio Grinstein
Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane...
March 19, 2018: ELife
Yunuen Avalos-Padilla, Roland L Knorr, Rosario Javier-Reyna, Guillermina García-Rivera, Reinhard Lipowsky, Rumiana Dimova, Esther Orozco
The endosomal sorting complex required for transport (ESCRT) orchestrates cell membrane-remodeling mechanisms in eukaryotes, including endocytosis. However, ESCRT functions in phagocytosis (ingestion of ≥250 nm particles), has been poorly studied. In macrophages and amoebae, phagocytosis is required for cell nutrition and attack to other microorganisms and cells. In Entamoeba histolytica , the voracious protozoan responsible for human amoebiasis, phagocytosis is a land mark of virulence. Here, we have investigated the role of ESCRT-III in the phagocytosis of E...
2018: Frontiers in Cellular and Infection Microbiology
Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the β2 integrin Mac-1 (CR3, integrin αM β2 ), a receptor recognizing diverse microbial ligands...
March 14, 2018: Cell Host & Microbe
Danielle M Clancy, Graeme P Sullivan, Hannah B T Moran, Conor M Henry, Emer P Reeves, Noel G McElvaney, Ed C Lavelle, Seamus J Martin
Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil proteases play an important role in the coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines are important initiators of inflammation and are typically released via necrosis but require proteolytic processing for activation...
March 13, 2018: Cell Reports
Christopher J Anderson, John Satkovich, Volkan K Köseoğlu, Hervé Agaisse, Melissa M Kendall
Ethanolamine is a ubiquitous and essential molecule within a host. Significantly, bacterial pathogens exploit ethanolamine during infection to promote growth and regulate virulence. The ethanolamine permease EutH is dispensable for growth in vitro under standard conditions, whereas EutH is required for ethanolamine utilization at low pH. These findings suggested a model in which EutH facilitates diffusion of ethanolamine into the bacterial cell in acidic environments. To date, the ecological significance of this model has not been thoroughly investigated, and the importance of EutH to bacterial growth under physiologically relevant conditions is not known...
March 12, 2018: Infection and Immunity
Nicoleta T Ploscariu, Nienke W M de Jong, Kok P M van Kessel, Jos A G van Strijp, Brian V Geisbrecht
Staphylococcus aureus and related species are highly adapted to their hosts and have evolved numerous strategies to evade the immune system. S. aureus shows resistance to killing following uptake into the phagosome, which suggests that the bacterium evades intracellular killing mechanisms used by neutrophils. We recently discovered an S. aureus protein (SPIN for Staphylococcal Peroxidase INhibitor) that binds to and inhibits myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. To allow for comparative studies between multiple SPIN sequences, we identified a panel of homologs from species closely related to S...
March 7, 2018: Archives of Biochemistry and Biophysics
Razieh Rabani, Allen Volchuk, Mirjana Jerkic, Lindsay Ormesher, Linda Garces-Ramirez, Johnathan Canton, Claire Masterson, Stephane Gagnon, Kate C Tatham, John Marshall, Sergio Grinstein, John G Laffey, Katalin Szaszi, Gerard F Curley
Human Mesenchymal Stem/Stromal Cells (MSCs) have been reported to produce an M2-like, alternatively activated phenotype in macrophages. In addition, MSCs mediate effective bacterial clearance in pre-clinical sepsis models. Thus, MSCs have a paradoxical anti-microbial and anti-inflammatory response that is not understood. Here we studied the phenotypic and functional response of monocyte-derived human macrophages to MSC exposure in vitro MSCs induced two distinct, co-existent phenotypes: M2-like macrophages (generally elongated morphology, CD163 positive, acute phagosomal acidification, low NADPH oxidase expression and low phagosomal superoxide production) and M1-like macrophages, characterised by high levels of phagosomal superoxide production...
March 8, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Mingxing Yang, Maxie Kohler, Tina Heyder, Helena Forsslund, Hilde K Garberg, Reza Karimi, Johan Grunewald, Frode S Berven, C Magnus Sköld, Åsa M Wheelock
BACKGROUND: Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). METHODS: To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort...
March 8, 2018: Respiratory Research
Rachel E Polando, Blake C Jones, Cristina Ricardo, James Whitcomb, Wibke Ballhorn, Mary Ann McDowell
AIMS: Leishmania enter macrophages through receptor mediated phagocytosis and survive the harsh environment of a phagolysosome. Here, we investigated the interaction between MR, TLR2, and Leishmania, and the subsequent impact on phagosome maturation. METHODS AND RESULTS: Leishmania parasites are able to delay phagosome maturation, not reaching full maturation until five hours post engulfment. Here, maturation of Leishmania major and L. donovani containing phagosomes proceeded as expected in the WT macrophages becoming LAMP1 positive by 6 hours...
March 6, 2018: Parasite Immunology
Jing Gao, Yuhong Li, Tongmei Wang, Zhuo Shi, Yiqi Zhang, Shuang Liu, Pushuai Wen, Chunyan Ma
The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray dataset GSE5500 and GSE18801 were downloaded from GEO database, and differentially expressed genes (DEGs) were screened using Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using DAVID database. Furthermore, the top DEGs were further validated using qPCR in the hypertrophic heart tissue induced by Isoprenaline (ISO). A total of 113 common DEGs with absolute fold change >0...
March 6, 2018: Canadian Journal of Physiology and Pharmacology
Marcel D O Pinheiro, Niels C Bols
For the first time, ciliates have been found to activate rather than inactivate a virus, chum salmon reovirus (CSV). Activation was seen as an increase in viral titre upon incubation of CSV at 22 °C with Tetrahymena canadenesis and two strains of T. thermophila: wild type (B1975) and a temperature conditional mutant for phagocytosis (NP1). The titer increase was not likely due to replication because CSV had no visible effects on the ciliates and no vertebrate virus has ever been shown unequivocally to replicate in ciliates...
March 5, 2018: Journal of Eukaryotic Microbiology
Amaliya Stepanova, Natalia Vasilyeva, Masashi Yamaguchi, Hiroji Chibana, Iliya Bosak, Larisa Filippova
This article presents the ultrastructural patterns of interactions between the murine lung macrophages and cells of low- (RKPGY-881, -1165, -1178) and high-virulence (RKPGY-1090, -1095, -1106) strains of Cryptococcus neoformans at the seventh post-experimental day. It was found that if macrophages ingest living yeast cells, the latter can: 1) become completely free from polysaccharide capsules, after that their contents undergo lysis, and cell wall debris are extruded from the macrophage (first scenario); 2) become partly free from their capsules, destroy the phagosomal plasma membrane and induce destructive processes inside the macrophage causing their death (second scenario); or 3) not lose their capsules and localize inside macrophage in latent state (third scenario)...
2018: Medical Mycology Journal
Taylor S Cohen, Michelle L Boland, Brandon B Boland, Virginia Takahashi, Andrey Tovchigrechko, Young Lee, Aimee D Wilde, Mark J Mazaitis, Omari Jones-Nelson, Christine Tkaczyk, Rajiv Raja, C Kendall Stover, Bret R Sellman
Clinical severity of Staphylococcus aureus respiratory infection correlates with alpha toxin (AT) expression. AT activates the NLRP3 inflammasome; deletion of Nlrp3, or AT neutralization, protects mice from lethal S. aureus pneumonia. We tested the hypothesis that this protection is not due to a reduction in inflammasome-dependent cytokines (IL-1β/IL-18) but increased bactericidal function of macrophages. In vivo, neutralization of AT or NLRP3 improved bacterial clearance and survival, while blocking IL-1β/IL-18 did not...
February 27, 2018: Cell Reports
Nikita H Trivedi, Jieh-Juen Yu, Chiung-Yu Hung, Richard P Doelger, Christopher S Navara, Lisa Y Armitige, Janakiram Seshu, Anthony P Sinai, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection...
January 1, 2018: Innate Immunity
Eloise Keeling, Andrew J Lotery, David A Tumbarello, J Arjuna Ratnayaka
Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways lead to the accumulation of lipofuscin and pyridinium bis-retinoid A2E aggregates and chemically modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE...
February 23, 2018: Cells
Florence Niedergang, Sergio Grinstein
Phagocytosis is a complex and elegant mechanism requiring finely coordinated deformation and restructuring of the membrane and the underlying cytoskeleton. Here we discuss the early events of receptor clustering and engagement required for signal transduction and actin remodeling. In addition, we summarize recent studies of the mechanisms whereby the nascent phagosome seals and evolves into a degradative phagolysosome by a process that seemingly involves the autophagic machinery. These studies provided new insights of the molecular basis of this long-appreciated, essential homeostatic process...
February 19, 2018: Current Opinion in Cell Biology
Amanda Souza Câmara, Eduardo Horjales
M. tuberculosis oxidation sense Regulator (MosR) is a transcriptional regulator from Mycobacterium tuberculosis. It senses the environment oxidation and regulates the expression of a secreted oxidoreductase, thus defending the bacilli against oxidative stress from the phagosome. While most of the members of the Multiple antibiotics resistance Regulator (MarR) family are ligand-responsive, MosR may dissociate from its DNA site upon formation of an intrachain disulphide bond. However, the structure of MosR in its oxidized state is not known, and it is not clear how the formation of this disulphide bond would lead to the conformational changes required for dissociation of the DNA...
2018: PloS One
Michael G Connor, Amanda R Pulsifer, Donghoon Chung, Eric C Rouchka, Brian K Ceresa, Matthew B Lawrenz
Yersinia pestis has evolved many strategies to evade the innate immune system. One of these strategies is the ability to survive within macrophages. Upon phagocytosis, Y. pestis prevents phagolysosome maturation and establishes a modified compartment termed the Yersinia -containing vacuole (YCV). Y. pestis actively inhibits the acidification of this compartment, and eventually, the YCV transitions from a tight-fitting vacuole into a spacious replicative vacuole. The mechanisms to generate the YCV have not been defined...
February 20, 2018: MBio
Roberto Nisini, Noemi Poerio, Sabrina Mariotti, Federica De Santis, Maurizio Fraziano
Liposomes are closed bilayer structures spontaneously formed by hydrated phospholipids that are widely used as efficient delivery systems for drugs or antigens, due to their capability to encapsulate bioactive hydrophilic, amphipathic, and lipophilic molecules into inner water phase or within lipid leaflets. The efficacy of liposomes as drug or antigen carriers has been improved in the last years to ameliorate pharmacokinetics and capacity to release their cargo in selected target organs or cells. Moreover, different formulations and variations in liposome composition have been often proposed to include immunostimulatory molecules, ligands for specific receptors, or stimuli responsive compounds...
2018: Frontiers in Immunology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"