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neutrophils starvation

Cheryl-Lynn Y Ong, Olga Berking, Mark J Walker, Alastair G McEwan
Zinc plays an important role in host innate immune function. However, the innate immune system also utilizes zinc starvation ('nutritional immunity') to combat infections. Here, we investigate the role of zinc import and export in protection of Streptococcus pyogenes (Group A Streptococcus ; GAS), a Gram-positive bacterial pathogen responsible for a wide spectrum of human diseases, against challenge from host innate immune defence. In order to determine the role of GAS zinc import and export during infection, we utilized the zinc import (Δ adcA/AII ) and export (Δ czcD ) deletion mutants in competition with wild-type in both in vitro and in vivo virulence models...
March 26, 2018: Infection and Immunity
Daniel J Becker, Gábor Á Czirják, Dmitriy V Volokhov, Alexandra B Bentz, Jorge E Carrera, Melinda S Camus, Kristen J Navara, Vladimir E Chizhikov, M Brock Fenton, Nancy B Simmons, Sergio E Recuenco, Amy T Gilbert, Sonia Altizer, Daniel G Streicker
Human activities create novel food resources that can alter wildlife-pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria...
May 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Leonardo Iula, Irene A Keitelman, Florencia Sabbione, Federico Fuentes, Mauricio Guzman, Jeremías Gastón Galletti, Pehuén Pereyra Gerber, Matías Ostrowski, Jorge R Geffner, Carolina C Jancic, Analía S Trevani
Interleukin-1β (IL-1β), a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions...
2018: Frontiers in Immunology
Anita Leocadio Freitas-Mesquita, José Roberto Meyer-Fernandes
3'-nucleotidase/nuclease (3'NT/NU) is a bi-functional enzyme that is able to hydrolyze 3'-monophosphorylated nucleotides and nucleic acids. This review summarizes the major molecular and biochemical properties of this enzyme in different trypanosomatid species. Sequence analysis of the gene encoding 3'NT/NU in Leishmania and Crithidia species showed that the protein possesses five highly conserved regions that are characteristic of members of the class I nuclease family. 3'NT/NU presents a molecular weight of approximately 40 kDa, which is conserved among the studied species...
August 2017: Experimental Parasitology
Monika A Krezalek, Sanjiv Hyoju, Alexander Zaborin, Emeka Okafor, Laxmi Chandrasekar, Vitas Bindokas, Kristina Guyton, Christopher P Montgomery, Robert S Daum, Olga Zaborina, Susan Boyle-Vavra, John C Alverdy
OBJECTIVE: To determine whether intestinal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be the source of surgical site infections (SSIs). BACKGROUND: We hypothesized that gut-derived MRSA may cause SSIs via mechanisms in which circulating immune cells scavenge MRSA from the gut, home to surgical wounds, and cause infection (Trojan Horse Hypothesis). METHODS: MRSA gut colonization was achieved by disrupting the microbiota with antibiotics, imposing a period of starvation and introducing MRSA via gavage...
February 9, 2017: Annals of Surgery
Federico Pietrocola, Yohann Demont, Francesca Castoldi, David Enot, Sylvère Durand, Michaela Semeraro, Elisa Elena Baracco, Jonathan Pol, Jose Manuel Bravo-San Pedro, Chloé Bordenave, Sarah Levesque, Juliette Humeau, Alexis Chery, Didier Métivier, Frank Madeo, M Chiara Maiuri, Guido Kroemer
Starvation is a strong physiological stimulus of macroautophagy/autophagy. In this study, we addressed the question as to whether it would be possible to measure autophagy in blood cells after nutrient deprivation. Fasting of mice for 48 h (which causes ∼20% weight loss) or starvation of human volunteers for up to 4 d (which causes <2% weight loss) provokes major changes in the plasma metabolome, yet induces only relatively minor alterations in the intracellular metabolome of circulating leukocytes. White blood cells from mice and human volunteers responded to fasting with a marked reduction in protein lysine acetylation, affecting both nuclear and cytoplasmic compartments...
March 4, 2017: Autophagy
Bianca Schwartbeck, Johannes Birtel, Janina Treffon, Lars Langhanki, Alexander Mellmann, Devika Kale, Janina Kahl, Nina Hirschhausen, Claudia Neumann, Jean C Lee, Friedrich Götz, Holger Rohde, Hanae Henke, Peter Küster, Georg Peters, Barbara C Kahl
Cystic fibrosis (CF) is associated with chronic bacterial airway infections leading to lung insufficiency and decreased life expectancy. Staphylococcus aureus is one of the most prevalent pathogens isolated from the airways of CF patients. Mucoid colony morphology has been described for Pseudomonas aeruginosa, the most common pathogen in CF, but not for S. aureus. From the airways of 8 of 313 CF patients (2.5%) mucoid S. aureus isolates (n = 115) were cultured with a mean persistence of 29 months (range 1 month, 126 months)...
November 2016: PLoS Pathogens
Mirjana Jerkic, Michelle Letarte
Endoglin (ENG) is a TGF-β superfamily coreceptor essential for vascular endothelium integrity. ENG mutations lead to a vascular dysplasia associated with frequent hemorrhages in multiple organs, whereas ENG null mouse embryos die at midgestation with impaired heart development and leaky vasculature. ENG interacts with several proteins involved in cell adhesion, and we postulated that it regulates vascular permeability. The current study assessed the permeability of ENG homozygous null (Eng(-/-)), heterozygous (Eng(+/-)), and normal (Eng(+/+)) mouse embryonic endothelial cell (EC) lines...
September 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Andrew G Turner, Cheryl-Lynn Y Ong, Christine M Gillen, Mark R Davies, Nicholas P West, Alastair G McEwan, Mark J Walker
UNLABELLED: Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence...
2015: MBio
Alina Aguirre, Inés López-Alonso, Adrián González-López, Laura Amado-Rodríguez, Estefanía Batalla-Solís, Aurora Astudillo, Jorge Blázquez-Prieto, Alvaro F Fernández, José A Galván, Claudia C dos Santos, Guillermo M Albaiceta
UNLABELLED: Autophagy has emerged as a key regulator of the inflammatory response. To examine the role of autophagy in the development of organ dysfunction during endotoxemia, wild-type and autophagy-deficient (Atg4b-null) mice were challenged with lipopolysaccharide. Animals lacking Atg4b showed increased mortality after endotoxemia. Among the different organs studied, only the lungs showed significant differences between genotypes, with increased damage in mutant animals. Autophagy was activated in lungs from wild-type, LPS-treated mice...
June 2014: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Sylvia Simon, Maria A Wagner, Eva Rothmeier, Annette Müller-Taubenberger, Hubert Hilbi
The environmental bacterium Legionella pneumophila causes a severe pneumonia termed Legionnaires' disease. L. pneumophila employs a conserved mechanism to replicate within a specific vacuole in macrophages or protozoa such as the social soil amoeba Dictyostelium discoideum. Pathogen-host interactions depend on the Icm/Dot type IV secretion system (T4SS), which translocates approximately 300 different effector proteins into host cells. Here we analyse the effects of L. pneumophila on migration and chemotaxis of amoebae, macrophages or polymorphonuclear neutrophils (PMN)...
July 2014: Cellular Microbiology
Fraser D Russell, Karina D Hamilton
Nutrient deprivation is a stimulus for oxidative stress and is an established method for induction of cell autophagy and apoptosis. The aims of this study were to identify conditions that evoke superoxide production in cultured human umbilical vein endothelial cells (HUVECs), determine the mechanism of action for this response, and examine whether the stimulus might facilitate the adhesion of human isolated neutrophils to the HUVECs. HUVECs were incubated in M199 medium under conditions of serum starvation (serum-free M199 medium), low serum (medium containing 2% fetal calf serum), and high serum (medium containing 20% fetal calf serum)...
February 2014: Free Radical Biology & Medicine
Jin Wang, Xiangmei Zhou, Bo Pan, Lifeng Yang, Xiaomin Yin, Binrui Xu, Deming Zhao
Bovine tuberculosis is a disease in cattle caused by infection with Mycobacterium bovis. The disease has posed significant economic losses and remains a public health hazard worldwide. Interactions between M. bovis and bovine macrophages have been extensively characterized in various studies, while similar analyses in neutrophils, which are one of the other types of white blood cells in mammals, were often overlooked. Neutrophils provide defense against all microbes and can present a diverse collection of antimicrobial molecules, which play an important role in the control of tuberculosis progression...
November 2013: Tuberculosis
Pedro Miramón, Christine Dunker, Hanna Windecker, Iryna M Bohovych, Alistair J P Brown, Oliver Kurzai, Bernhard Hube
Neutrophils are key players during Candida albicans infection. However, the relative contributions of neutrophil activities to fungal clearance and the relative importance of the fungal responses that counteract these activities remain unclear. We studied the contributions of the intra- and extracellular antifungal activities of human neutrophils using diagnostic Green Fluorescent Protein (GFP)-marked C. albicans strains. We found that a carbohydrate starvation response, as indicated by up-regulation of glyoxylate cycle genes, was only induced upon phagocytosis of the fungus...
2012: PloS One
Abderrahman Chargui, Annabelle Cesaro, Sanda Mimouna, Mohamed Fareh, Patrick Brest, Philippe Naquet, Arlette Darfeuille-Michaud, Xavier Hébuterne, Baharia Mograbi, Valérie Vouret-Craviari, Paul Hofman
Invading bacteria are recognized, captured and killed by a specialized form of autophagy, called xenophagy. Recently, defects in xenophagy in Crohn's disease (CD) have been implicated in the pathogenesis of human chronic inflammatory diseases of uncertain etiology of the gastrointestinal tract. We show here that pathogenic adherent-invasive Escherichia coli (AIEC) isolated from CD patients are able to adhere and invade neutrophils, which represent the first line of defense against bacteria. Of particular interest, AIEC infection of neutrophil-like PLB-985 cells blocked autophagy at the autolysosomal step, which allowed intracellular survival of bacteria and exacerbated interleukin-8 (IL-8) production...
2012: PloS One
Yoon Shin Park, Goh-Woon Lim, Kyung-Ah Cho, So-Youn Woo, Meeyoung Shin, Eun-Sun Yoo, Jeong Chan Ra, Kyung-Ha Ryu
Neutropenia is a principal complication of cancer treatment. We investigated the supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on the viability and function of neutrophils. Neutrophils were derived from HL-60 cells by dimethylformamide stimulation and cultured with or without AD-MSCs under serum-starved conditions to evaluate neutrophil survival, proliferation, and function. Serum starvation resulted in the apoptosis of neutrophils and decreased cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell survival and inhibited neutrophil apoptosis under serum-starved conditions...
June 22, 2012: Biochemical and Biophysical Research Communications
Gayathri Subramanian, Pulkit Chaudhury, Krishnakumar Malu, Samantha Fowler, Rahul Manmode, Deepali Gotur, Monika Zwerger, David Ryan, Rita Roberti, Peter Gaines
Lamin B receptor (LBR) is a bifunctional nuclear membrane protein with N-terminal lamin B and chromatin-binding domains plus a C-terminal sterol Δ(14) reductase domain. LBR expression increases during neutrophil differentiation, and deficient expression disrupts neutrophil nuclear lobulation characteristic of Pelger-Huët anomaly. Thus, LBR plays a critical role in regulating myeloid differentiation, but how the two functional domains of LBR support this role is currently unclear. We previously identified abnormal proliferation and deficient functional maturation of promyelocytes (erythroid, myeloid, and lymphoid [EML]-derived promyelocytes) derived from EML-ic/ic cells, a myeloid model of ichthyosis (ic) bone marrow that lacks Lbr expression...
January 1, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
Christopher A McDevitt, Abiodun D Ogunniyi, Eugene Valkov, Michael C Lawrence, Bostjan Kobe, Alastair G McEwan, James C Paton
Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumoniae extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude...
November 2011: PLoS Pathogens
Xuehua Xu, Tian Jin
Many eukaryotic cells can detect gradients of chemical signals in their environments and migrate accordingly (1). This guided cell migration is referred as chemotaxis, which is essential for various cells to carry out their functions such as trafficking of immune cells and patterning of neuronal cells (2, 3). A large family of G-protein coupled receptors (GPCRs) detects variable small peptides, known as chemokines, to direct cell migration in vivo (4). The final goal of chemotaxis research is to understand how a GPCR machinery senses chemokine gradients and controls signaling events leading to chemotaxis...
2011: Journal of Visualized Experiments: JoVE
Jimena Alvarez Hayes, Esteban Erben, Yanina Lamberti, Miguel Ayala, Fabricio Maschi, Cecilia Carbone, Blanca Gatti, Gustavo Parisi, Maria Eugenia Rodriguez
Antigenic proteins whose expression is induced under iron starvation, an environmental condition that bacterial pathogens have to face during colonization, might be potential candidates for improved vaccine. By mean of immune proteomics we identified novel antigens of Bordetella pertussis maximally expressed under iron limitation. Among them, Bp1152 (named as IRP1-3) showed a particularly strong reaction with human IgG purified from pooled sera of pertussis-infected individuals. Computer analysis showed IRP1-3 as a dimeric membrane protein potentially involved in iron uptake...
November 3, 2011: Vaccine
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