Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis.

Abstract:

:We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. tularensis live vaccine strain (LVS) caused significant changes in neutrophil gene expression over a 24-hour time period relative to the uninfected controls. Of approximately 47,000 genes analyzed, 3,435 were significantly up- or downregulated by LVS, including 365 unique genes associated with apoptosis and cell survival. Specific targets in this category included genes asso-ciated with the intrinsic and extrinsic apoptotic pathways (CFLAR, TNFAIP3, TNFRSF10D, SOD2, BCL2A1, BIRC4, PIM2, TNFSF10, TNFRSF10C, CASP2 and CASP8) and genes that act via the NFĸB pathway and other mechanisms to prolong cell viability (NFKB1, NFKB2 and RELA, IL1B, CAST, CDK2,GADD45B, BCL3, BIRC3, CDK2, IL1A, PBEF1, IL6, CXCL1, CCL4 and VEGF). The microarray data were confirmed by qPCR and pathway analysis. Moreover, we demonstrate that the X-linked inhibitor of apoptosis protein remained abundant in polymorphonuclear leukocytes over 48 h of LVS infection, whereas BAX mRNA and protein were progressively downregulated. These data strongly suggest that antiapoptotic and prosurvival mechanisms collaborate to sustain the viability of F. tularensis--infected neutrophils.

journal_name

J Innate Immun

authors

Schwartz JT,Bandyopadhyay S,Kobayashi SD,McCracken J,Whitney AR,Deleo FR,Allen LA

doi

10.1159/000342430

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

124-36

issue

2

eissn

1662-811X

issn

1662-8128

pii

000342430

journal_volume

5

pub_type

杂志文章
  • Aerobic Exercise Protects from Pseudomonas aeruginosa-Induced Pneumonia in Elderly Mice.

    abstract:BACKGROUND:Pseudomonas aeruginosa (PS) infection results in severe morbidity and mortality, especially in immune-deficient populations. Aerobic exercise (AE) modulates the immune system, but its effects on the outcomes of pulmonary PS infection in elderly mice are unknown. METHODS:BALB/c mice (24 weeks old) were rando...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000488953

    authors: Stravinskas Durigon T,MacKenzie B,Carneiro Oliveira-Junior M,Santos-Dias A,De Angelis K,Malfitano C,Kelly da Palma R,Moreno Guerra J,Damaceno-Rodrigues NR,Garcia Caldini E,de Almeida FM,Aquino-Santos HC,Rigonato-Oliveira NC,Lea

    更新日期:2018-01-01 00:00:00

  • Thrombospondin 1 Modulates Monocyte Properties to Suppress Intestinal Mucosal Inflammation.

    abstract::Monocytes (Mos) play an important role in the pathogenesis of intestinal mucosal inflammation. This study aims to investigate the mechanism by which the intestinal epithelial cell-derived thrombospondin 1 (TSP1) modulates Mo properties and regulates intestinal inflammatory responses. In this study, the production of T...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000398799

    authors: Fang LL,Yu HQ,Wu RJ,He C,Li M,Yan H,Li JJ,Wang S,Liu ZG,Liu ZJ,Yang PC

    更新日期:2015-01-01 00:00:00

  • PLA1A Participates in the Antiviral Innate Immune Response by Facilitating the Recruitment of TANK-Binding Kinase 1 to Mitochondria.

    abstract::As a key molecule in the antiviral innate immune response, the activation of TANK-binding kinase 1 (TBK1) is under tight regulation. In this report, we identified phosphatidylserine-specific phospholipase PLA1A as a host factor that modulates the TBK1 activation. Knockdown of PLA1A expression suppressed the innate imm...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000489832

    authors: Gao X,Chen D,Hu X,Zhou Y,Wang Y,Wu C,Chen J,Wang Y,Pei R,Chen X

    更新日期:2018-01-01 00:00:00

  • Calcium-independent phospholipase A2 beta is dispensable in inflammasome activation and its inhibition by bromoenol lactone.

    abstract::Calcium-independent phospholipase A2 (iPLA2) has been suggested to play an important role in the activation of caspase-1 induced by lipopolysaccharides (LPS). Here, we used pharmacological and genetic approaches to study the role of iPLA 2 in the activation of caspase-1. Bromoenol lactone (BEL), an inhibitor that was ...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000227263

    authors: Franchi L,Chen G,Marina-Garcia N,Abe A,Qu Y,Bao S,Shayman JA,Turk J,Dubyak GR,Núñez G

    更新日期:2009-01-01 00:00:00

  • Activation of the human contact system on neutrophil extracellular traps.

    abstract::Pattern recognition is an integral part of the innate immune system. The human contact system has been shown to interact with the surface of many bacterial and fungal pathogens, and once activated leads to the generation of antimicrobial peptides and the proinflammatory mediator bradykinin. Here we show that apart fro...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000203700

    authors: Oehmcke S,Mörgelin M,Herwald H

    更新日期:2009-01-01 00:00:00

  • The transcription factor nuclear factor of activated T cells c3 modulates the function of macrophages in sepsis.

    abstract::The role of the transcription factor nuclear factor of activated T cells (NFAT) was initially identified in T and B cell gene expression, but its role in regulating gene expression in macrophages during sepsis is not known. Our data show that NFATc3 regulates expression of inducible nitric oxide synthase (iNOS) in mac...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000362647

    authors: Ranjan R,Deng J,Chung S,Lee YG,Park GY,Xiao L,Joo M,Christman JW,Karpurapu M

    更新日期:2014-01-01 00:00:00

  • Anopheles stephensi Dual Oxidase Silencing Activates the Thioester-Containing Protein 1 Pathway to Suppress Plasmodium Development.

    abstract::We characterized the dual oxidase (Duox) gene in the major Indian malaria vector Anopheles stephensi, which regulates the generation of reactive oxygen species. The AsDuox gene encodes for a 1,475-amino-acid transmembrane protein that contains an N-terminal noncytoplasmic heme peroxidase domain, a calcium-binding doma...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000497417

    authors: Kakani P,Kajla M,Choudhury TP,Gupta L,Kumar S

    更新日期:2019-01-01 00:00:00

  • Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia.

    abstract::Klebsiella pneumoniae is a common cause of hospital-acquired pneumonia. Granzymes (gzms), mainly found in cytotoxic lymphocytes, have been implicated as mediators of infection and inflammation. We here sought to investigate the role of gzmA and gzmB in the host response to K. pneumoniae-induced airway infection and se...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000443401

    authors: García-Laorden MI,Stroo I,Blok DC,Florquin S,Medema JP,de Vos AF,van der Poll T

    更新日期:2016-01-01 00:00:00

  • Inhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1.

    abstract::Fibroblasts are known to eliminate intracellular bacteria, but the lethal hit of the bactericidal mechanism has not been defined. We show that primary embryonic and established fibroblasts can be induced by interferons or by intracellular bacterial infection to express a perforin-like mRNA previously described as macr...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000345249

    authors: McCormack R,de Armas LR,Shiratsuchi M,Ramos JE,Podack ER

    更新日期:2013-01-01 00:00:00

  • Systems biology of circadian-immune interactions.

    abstract::There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental d...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000342427

    authors: Mavroudis PD,Scheff JD,Calvano SE,Androulakis IP

    更新日期:2013-01-01 00:00:00

  • Specificity in killing pathogens is mediated by distinct repertoires of human neutrophil peptides.

    abstract::Neutrophil-derived antimicrobial peptides and proteins (AMPs) play an important role in the defense against microbes. Absence of defense is illustrated by neutropenic patients with frequent bacterial and fungal infections. However, the specificity of the antimicrobial effects has not been adequately described. We set ...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000317665

    authors: Cederlund A,Agerberth B,Bergman P

    更新日期:2010-01-01 00:00:00

  • The c-src homologue Src64B is sufficient to activate the Drosophila cellular immune response.

    abstract::The Drosophila larval cellular immune response involves cells (haemocytes) that can be recruited from a haematopoietic organ known as the lymph gland, as well as a sessile population of cells found just underneath the larval cuticle arranged in a segmental pattern. Overexpression of the Drosophila c-src homologue Src6...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000191216

    authors: Williams MJ

    更新日期:2009-01-01 00:00:00

  • Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer.

    abstract::Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000453594

    authors: van Putten JPM,Strijbis K

    更新日期:2017-01-01 00:00:00

  • Antiviral innate immunity disturbs podocyte cell function.

    abstract::Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis throughout the world. A majority (approx. 60%) of patients with IgAN experience disease exacerbations associated with an acute respiratory or gastrointestinal illness that appears to represent a viral infection. However, the exact mechan...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000345255

    authors: Yamashita M,Millward CA,Inoshita H,Saikia P,Chattopadhyay S,Sen GC,Emancipator SN

    更新日期:2013-01-01 00:00:00

  • The Drosophila deubiquitinating enzyme dUSP36 acts in the hemocytes for tolerance to Listeria monocytogenes infections.

    abstract::Listeria monocytogenes is a facultative intracellular pathogen which can infect Drosophila melanogaster. Upon infection, Drosophila mounts an immune response including antimicrobial peptide production and autophagy activation. A set of previously published results prompted us to study the role of the deubiquitinating ...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000360293

    authors: Taillebourg E,Schneider DS,Fauvarque MO

    更新日期:2014-01-01 00:00:00

  • Inositol phospholipid signaling and the biology of natural killer cells.

    abstract::A family of phosphoinositide-3 kinase (PI3K) isoenzymes catalyzes the production of second messengers that recruit critical regulators of cell growth, survival, proliferation and motility. Conversely, 3'-(phosphatase and tensin homolog) and 5'-inositol polyphosphatases (SH2-containing inositol phosphatases 1/2, SHIP1/...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000323920

    authors: Kerr WG,Colucci F

    更新日期:2011-01-01 00:00:00

  • Natural killer T cells and atherosclerosis: form and function meet pathogenesis.

    abstract::Atherosclerosis is a chronic inflammatory disease characterized by dyslipidemia and accumulation of lipids in the arterial intima, with activation of both innate and adaptive immunity. Reciprocally, dyslipidemia associated with atherosclerosis can perturb normal immune function. Natural killer T (NKT) cells are a spec...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000296915

    authors: Braun NA,Covarrubias R,Major AS

    更新日期:2010-01-01 00:00:00

  • Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD.

    abstract::There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as ne...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000509715

    authors: Stockfelt M,Christenson K,Andersson A,Björkman L,Padra M,Brundin B,Ganguly K,Asgeirsdottir H,Lindén S,Qvarfordt I,Bylund J,Lindén A

    更新日期:2020-01-01 00:00:00

  • The innate immune response: an important partner in shaping coxsackievirus-mediated autoimmunity.

    abstract::To protect against viral infection, the immune response is critically dependent on innate sensing mechanisms to provide rapid detection of pathogens and allow for the development of an appropriate adaptive immune response. Mounting evidence suggests that mechanistic differences in the sensing of viruses by the innate ...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000226247

    authors: Richer MJ,Horwitz MS

    更新日期:2009-01-01 00:00:00

  • Differential regulation by Toll-like receptor agonists reveals that MCPIP1 is the potent regulator of innate immunity in bacterial and viral infections.

    abstract::Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an im...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000339826

    authors: Blazusiak E,Florczyk D,Jura J,Potempa J,Koziel J

    更新日期:2013-01-01 00:00:00

  • HIV-1 Gag-virus-like particles induce natural killer cell immune responses via activation and maturation of dendritic cells.

    abstract::Despite the extensive efforts that have been made to combat acquired immune deficiency syndrome (AIDS), the number of people infected each year with human immunodeficiency virus type 1 (HIV-1) is still increasing worldwide, and a safe and effective vaccine to control HIV infection is urgently needed. Recently, the nat...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000329226

    authors: Chang MO,Suzuki T,Suzuki H,Takaku H

    更新日期:2012-01-01 00:00:00

  • Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during Acute Human Anaphylaxis: Validation of a Microarray Study.

    abstract:BACKGROUND:We have previously identified the upregulation of the innate immune response, neutrophil activation, and apoptosis during anaphylaxis using a microarray approach. This study aimed to validate the differential gene expression and investigate protein concentrations of "hub genes" and upstream regulators during...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000492301

    authors: Francis A,Bosio E,Stone SF,Fatovich DM,Arendts G,MacDonald SPJ,Burrows S,Brown SGA

    更新日期:2019-01-01 00:00:00

  • Antiviral activity of innate immune protein ISG15.

    abstract::The host innate immune response, including the production of type-I IFN, represents the primary line of defense against invading viral pathogens. Of the hundreds of IFN-stimulated genes (ISGs) discovered to date, ISG15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000226245

    authors: Harty RN,Pitha PM,Okumura A

    更新日期:2009-01-01 00:00:00

  • A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity.

    abstract:BACKGROUND:Alpha-synuclein (αS) is a nerve cell protein associated with Parkinson disease (PD). Accumulation of αS within the enteric nervous system (ENS) and its traffic from the gut to the brain are implicated in the pathogenesis and progression of PD. αS has no known function in humans and the reason for its accumul...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000477990

    authors: Stolzenberg E,Berry D,Yang,Lee EY,Kroemer A,Kaufman S,Wong GCL,Oppenheim JJ,Sen S,Fishbein T,Bax A,Harris B,Barbut D,Zasloff MA

    更新日期:2017-01-01 00:00:00

  • The domain organization of p67 phox, a protein required for activation of the superoxide-producing NADPH oxidase in phagocytes.

    abstract::The phagocyte NADPH oxidase, crucial for innate immunity, is dormant in resting cells, but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. In activation of the oxidase, the multidomain protein p67(phox)plays a central role: it translocates to the membrane as a ternary...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000235656

    authors: Yuzawa S,Miyano K,Honbou K,Inagaki F,Sumimoto H

    更新日期:2009-01-01 00:00:00

  • Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease.

    abstract::Neutrophils are the most abundant cell type involved in the innate immune response. They are rapidly recruited to sites of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil histotoxic contents, is t...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000284367

    authors: Fox S,Leitch AE,Duffin R,Haslett C,Rossi AG

    更新日期:2010-01-01 00:00:00

  • Killer immunoglobulin-like receptor transcriptional regulation: a fascinating dance of multiple promoters.

    abstract::Killer immunoglobulin-like receptors (KIRs) recognize class I major histocompatibility complex molecules and participate in the calibration of activation thresholds during human natural killer (NK) cell development. The stochastic expression pattern of the KIR repertoire follows the product rule, meaning that the prob...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000323929

    authors: Cichocki F,Miller JS,Anderson SK

    更新日期:2011-01-01 00:00:00

  • Syk Inhibitor Attenuates Polymicrobial Sepsis in FcgRIIb-Deficient Lupus Mouse Model, the Impact of Lupus Characteristics in Sepsis.

    abstract::The impact of spleen tyrosine kinase (Syk) signaling might be prominent in lupus because (i) Syk is a shared downstream signaling molecule among circulating immune complex, LPS, and (1→3)-β-D-glucan (BG), and (ii) all of these factors are detectable in the serum of Fc gamma receptor IIb-deficient (FcgRIIb-/-) mice wit...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000509111

    authors: Issara-Amphorn J,Chancharoenthana W,Visitchanakun P,Leelahavanichkul A

    更新日期:2020-01-01 00:00:00

  • Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia.

    abstract::Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapid...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章

    doi:10.1159/000447713

    authors: Armitage AE,Lim PJ,Frost JN,Pasricha SR,Soilleux EJ,Evans E,Morovat A,Santos A,Diaz R,Biggs D,Davies B,Gileadi U,Robbins PA,Lakhal-Littleton S,Drakesmith H

    更新日期:2016-01-01 00:00:00

  • Particulate systems for targeting of macrophages: basic and therapeutic concepts.

    abstract::Particulate systems in the form of liposomes, polymeric micelles, polymeric nano- and microparticles, and many others offer a rational approach for selective delivery of therapeutic agents to the macrophage from different physiological portals of entry. Particulate targeting of macrophages and intracellular drug relea...

    journal_title:Journal of innate immunity

    pub_type: 杂志文章,评审

    doi:10.1159/000339153

    authors: Moghimi SM,Parhamifar L,Ahmadvand D,Wibroe PP,Andresen TL,Farhangrazi ZS,Hunter AC

    更新日期:2012-01-01 00:00:00