Neutrophil antimicrobial defense against Staphylococcus aureus is mediated by phagolysosomal but not extracellular trap-associated cathelicidin.

Abstract:

:Neutrophils kill invading pathogens by AMPs, including cathelicidins, ROS, and NETs. The human pathogen Staphylococcus aureus exhibits enhanced resistance to neutrophil AMPs, including the murine cathelicidin CRAMP, in part, as a result of alanylation of teichoic acids by the dlt operon. In this study, we took advantage of the hypersusceptible phenotype of S. aureus DeltadltA against cationic AMPs to study the impact of the murine cathelicidin CRAMP on staphylococcal killing and to identify its key site of action in murine neutrophils. We demonstrate that CRAMP remained intracellular during PMN exudation from blood and was secreted upon PMA stimulation. We show first evidence that CRAMP was recruited to phagolysosomes in infected neutrophils and exhibited intracellular activity against S. aureus. Later in infection, neutrophils produced NETs, and immunofluorescence revealed association of CRAMP with S. aureus in NETs, which similarly killed S. aureus wt and DeltadltA, indicating that CRAMP activity was reduced when associated with NETs. Indeed, the presence of DNA reduced the antimicrobial activity of CRAMP, and CRAMP localization in response to S. aureus was independent of the NADPH oxidase, whereas killing was partially dependent on a functional NADPH oxidase. Our study indicates that neutrophils use CRAMP in a timed and locally coordinated manner in defense against S. aureus.

journal_name

J Leukoc Biol

authors

Jann NJ,Schmaler M,Kristian SA,Radek KA,Gallo RL,Nizet V,Peschel A,Landmann R

doi

10.1189/jlb.0209053

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1159-69

issue

5

eissn

0741-5400

issn

1938-3673

pii

jlb.0209053

journal_volume

86

pub_type

杂志文章
  • IL-10 receptor dysfunction in macrophages during chronic inflammation.

    abstract::The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected w...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Avdiushko R,Hongo D,Lake-Bullock H,Kaplan A,Cohen D

    更新日期:2001-10-01 00:00:00

  • Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of delta-PKC and ERK1/2.

    abstract::TNF is implicated in the suppression of neutrophil apoptosis during sepsis. Multiple signaling pathways are involved in TNF-mediated antiapoptotic signaling; a role for the MAP kinases (MAPK), ERK1/2, and p38 MAPK has been suggested. Antiapoptotic signaling is mediated principally through TNF receptor-1 (TNFR-1), and ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0406284

    authors: Kilpatrick LE,Sun S,Mackie D,Baik F,Li H,Korchak HM

    更新日期:2006-12-01 00:00:00

  • Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation.

    abstract::Human rhinovirus (HRV)-induced respiratory infections are associated with elevated levels of IFN-gamma-inducible protein 10 (IP-10), which is an enhancer of T lymphocyte chemotaxis and correlates with symptom severity and T lymphocyte number. Increased IP-10 expression is exhibited by airway epithelial cells following...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0606412

    authors: Korpi-Steiner NL,Bates ME,Lee WM,Hall DJ,Bertics PJ

    更新日期:2006-12-01 00:00:00

  • Differential regulation of TSG-14 expression in murine fibroblasts and peritoneal macrophages.

    abstract::Tumor necrosis factor (TNF)-stimulated gene 14 (TSG-14, also termed PTX3) encodes a secreted glycoprotein whose carboxy-terminal half shares sequence similarity with the pentraxin family of acute phase proteins (C-reactive protein and serum amyloid P component). We compared TSG-14 mRNA expression in cultures of murine...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.67.3.387

    authors: Goodman AR,Levy DE,Reis LF,Vilcek J

    更新日期:2000-03-01 00:00:00

  • A direct signaling pathway through tyrosine kinase activation of SH2 domain-containing transcription factors.

    abstract::Studies on the mechanism of interferon-induced gene expression revealed a direct signaling pathway from cell surface receptors to transcription factors. In this pathway, signal transduction is mediated by a new class of transcription factor STAT (signal transducer and activator of transcription). We have shown that ST...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.57.4.529

    authors: Fu XY

    更新日期:1995-04-01 00:00:00

  • IL-10 expression profiling in human monocytes.

    abstract::Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine with numerous immunomodulatory effects, including the inhibition of proinflammatory cytokine production. The mechanisms by which IL-10 exerts these effects still remain largely unknown. As there is evidence that suggests IL-10-mediated cytokine suppression ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Williams L,Jarai G,Smith A,Finan P

    更新日期:2002-10-01 00:00:00

  • LPS resistance in monocytic cells caused by reverse signaling through transmembrane TNF (mTNF) is mediated by the MAPK/ERK pathway.

    abstract::The transmembrane form of tumor necrosis factor (mTNF), expressed on activated monocytes (MO) and macrophages (MPhi), is able to induce apoptosis in human endothelial cells (EC). Apoptosis is mediated by two distinct mechanisms: direct cell contact and a yet-unidentified soluble protein, death factor X. In addition, m...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0703343

    authors: Kirchner S,Boldt S,Kolch W,Haffner S,Kazak S,Janosch P,Holler E,Andreesen R,Eissner G

    更新日期:2004-02-01 00:00:00

  • Myeloid-derived suppressor cells and their association with vaccine immunogenicity in South African infants.

    abstract::The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood s...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.5A0420-281R

    authors: Kidzeru E,Gasper MA,Shao D,Edlefsen PT,Lejarcegui N,Havyarimana E,Urdahl K,Gantt S,Horton H,Jaspan H,Gervassi A

    更新日期:2021-01-21 00:00:00

  • Type I interferon production in HIV-infected patients.

    abstract::Type I IFNs display multiple biological effects. They have a strong antiviral action, not only directly but also indirectly through activation of the immune system. They may also have actions that are deleterious for the host. The cells that produce type I IFN are mostly plasmacytoid dendritic cells (pDC), but this de...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0306154

    authors: Hosmalin A,Lebon P

    更新日期:2006-11-01 00:00:00

  • Relative role of chloramines, hypochlorous acid, and proteases in the activation of human polymorphonuclear leukocyte collagenase.

    abstract::The activation of collagenase released by polymorphonuclear leukocytes (PMNs) has been extensively studied in vitro, but the activation of the enzyme in vivo is not fully understood. For further evaluation of the relative role of oxidative and proteolytic mechanisms in the activation of collagenase, PMNs were stimulat...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.60.5.598

    authors: Claesson R,Karlsson M,Zhang Y,Carlsson J

    更新日期:1996-11-01 00:00:00

  • Pivotal Advance: Protein synthesis modulates responsiveness of differentiating and malignant plasma cells to proteasome inhibitors.

    abstract::A previously unsuspected, considerable proportion of newly synthesized polypeptides are hydrolyzed rapidly by proteasomes, possibly competing with endogenous substrates and altering proteostasis. In view of the anti-cancer effects of PIs, we set out to achieve a quantitative assessment of proteasome workload in cells ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1011497

    authors: Cenci S,Oliva L,Cerruti F,Milan E,Bianchi G,Raule M,Mezghrani A,Pasqualetto E,Sitia R,Cascio P

    更新日期:2012-11-01 00:00:00

  • A new monoclonal antibody, TRPM-3, binds specifically to certain rat macrophage populations: immunohistochemical and immunoelectron microscopic analysis.

    abstract::An anti-macrophage monoclonal antibody designated TRPM-3 was produced using thioglycollate-elicited rat peritoneal macrophages as immunogen. By the immunoperoxidase method, TRPM-3 was found to be specific for certain macrophage populations, such as marginal zone macrophages and marginal metallophils of the spleen, sin...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.41.3.187

    authors: Takeya M,Hsiao L,Takahashi K

    更新日期:1987-03-01 00:00:00

  • Phospholipase D mediates Fc gamma receptor activation of neutrophils and provides specificity between high-valency immune complexes and fMLP signaling pathways.

    abstract::Neutrophils phagocytize high-valency immune complexes (HIC) by an Fc gamma receptor-mediated mechanism, activating an oxidative burst and initiating degranulation. In contrast, neutrophils exhibit chemotaxis to N-formylated peptides [e.g., N-formyl-methionyl-leucyl-phenylalanine (fMLP)] and secrete far fewer oxidants ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.61.4.522

    authors: Gewirtz AT,Simons ER

    更新日期:1997-04-01 00:00:00

  • Noncanonical dendritic cell differentiation and survival driven by a bacteremic pathogen.

    abstract::Maintenance of blood DC homeostasis is essential to preventing autoimmunity while controlling chronic infection. However, the ability of bacteremic pathogens to directly regulate blood DC homeostasis has not been defined. One such bacteremic pathogen, Porphyromonas gingivalis, is shown by our group to survive within m...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0213108

    authors: Miles B,Scisci E,Carrion J,Sabino GJ,Genco CA,Cutler CW

    更新日期:2013-08-01 00:00:00

  • Actin polymerization contributes to neutrophil chemotactic dysfunction following thermal injury.

    abstract::The agent(s) and mechanism(s) responsible for suppression of neutrophil chemotaxis in association with major thermal injury have not been identified. We have proposed that the reduced random motility characterizing patients' cells may contribute to their generalized chemotactic dysfunction. Here we report that actin p...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.52.5.495

    authors: Hasslen SR,Ahrenholz DH,Solem LD,Nelson RD

    更新日期:1992-11-01 00:00:00

  • The functions of EZH2 in immune cells: Principles for novel immunotherapies.

    abstract::Enhancer of zeste homolog 2 (EZH2) is aberrantly expressed or mutated in multiple types of cancer cells and plays an oncogenic role in tumorigenesis and development in most cancers. Results from pilot clinical studies have implied that EZH2 inhibitors have therapeutic potential against some cancers. However, the exact...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/JLB.1RU0520-311R

    authors: Shao FF,Chen BJ,Wu GQ

    更新日期:2020-10-11 00:00:00

  • Flow cytometric analysis of I-J expression on murine bone marrow-derived macrophages.

    abstract::Attempts to analyze bone marrow-derived macrophages (BMDM) by flow cytometry have been prohibited because of their high autofluorescence. Using an autofluorescence reduction method of Steinkamp and Stewart to reduce the autofluorescence of BMDM, we were able to examine several macrophage populations for their expressi...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.43.6.557

    authors: Malley A,Stewart CC,Stewart SJ,Waldbeser L,Bradley LM,Shiigi SM

    更新日期:1988-06-01 00:00:00

  • Metabolic energy sensors as targets for designing host-directed therapies for tuberculosis.

    abstract::A wealth of scientific and clinical evidence during the past few years has lent credence to the idea that key components of the host immune effector mechanisms can be targeted to boost current tuberculosis (TB) treatment and control patient relapse. These host-directed strategies not only accelerate the clearance of p...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.4MR0617-226R

    authors: Cheng CY,Böhme J,Singhal A

    更新日期:2018-02-01 00:00:00

  • Analysis of the synergistic stimulation of mouse macrophage proliferation by macrophage colony-stimulating factor (CSF-1) and tumor necrosis factor alpha (TNF-alpha).

    abstract::Tumor necrosis factor alpha (TNF-alpha) more than doubles tritiated thymidine ([3H]TdR) uptake in mouse macrophages stimulated by macrophage colony-stimulating factor (CSF-1). However, nothing is known of how TNF-alpha affects this increase or even whether it is manifested by increased cellular proliferation. Here we ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.54.1.65

    authors: Guilbert LJ,Winkler-Lowen B,Smith A,Branch DR,Garcia-Lloret M

    更新日期:1993-07-01 00:00:00

  • C1qR(P), a myeloid cell receptor in blood, is predominantly expressed on endothelial cells in human tissue.

    abstract::C1qR(P) is a type I cell surface glycoprotein that has been shown to enhance ingestion of suboptimally opsonized targets by phagocytes in vitro. In this study, we developed and characterized polyclonal antibodies to study the tissue distribution of this receptor targeted to either the N- or C-terminal portion of the m...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Fonseca MI,Carpenter PM,Park M,Palmarini G,Nelson EL,Tenner AJ

    更新日期:2001-11-01 00:00:00

  • Dual role of macrophages in tumor growth and angiogenesis.

    abstract::During the neoplastic progression, macrophages as well as dendritic and NK cells are attracted into the tumor site and initiate the immune response against transformed cells. They activate and present tumor antigens to T cells, which are then activated to kill tumor cells. However, tumor cells are often capable of esc...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.1105656

    authors: Lamagna C,Aurrand-Lions M,Imhof BA

    更新日期:2006-10-01 00:00:00

  • Modulation of neutrophil migration by exogenous gaseous nitric oxide.

    abstract::We studied the effect of exogenous nitric oxide (NO) on migration of rabbit peritoneal neutrophils. Exogenous NO enhanced random migration of neutrophils in a concentration-dependent way. An optimally stimulatory effect was observed with 0.5 microM NO, whereas at higher NO concentrations the enhancing effect decreased...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.60.1.94

    authors: VanUffelen BE,de Koster BM,Van den Broek PJ,VanSteveninck J,Elferink JG

    更新日期:1996-07-01 00:00:00

  • Dap12 expression in activated microglia from retinoschisin-deficient retina and its PU.1-dependent promoter regulation.

    abstract::Several alterations in the expression of immune-related transcripts were identified recently in the degenerating retina of the retinoschisin knockout (Rs1h(-/Y)) mouse, including the strong expression of the adaptor protein Dap12. As Dap12 is found in leukocytes, we hypothesized that its disease-related expression may...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0707447

    authors: Weigelt K,Ernst W,Walczak Y,Ebert S,Loenhardt T,Klug M,Rehli M,Weber BH,Langmann T

    更新日期:2007-12-01 00:00:00

  • The bone marrow: a site of neutrophil clearance.

    abstract::Neutrophils, an essential component of the innate immune system, are produced at a rate 10(11) cells/day and are consequently the most abundant leukocyte in the blood. These granulocytes have a relatively short half-life (6-8 h) in the blood, and as a result of the cytotoxic nature of their contents, it is critical th...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0210112

    authors: Rankin SM

    更新日期:2010-08-01 00:00:00

  • Frontline Science: Coincidental null mutation of Csf2rα in a colony of PI3Kγ-/- mice causes alveolar macrophage deficiency and fatal respiratory viral infection.

    abstract::PI3Ks have been identified as key signaling proteins involved in many basic biologic processes in health and disease. Transgenic animals have been essential tools to study the underlying molecular mechanisms in this context and therefore, have been widely used to elucidate the role of these factors in many different s...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.4HI0316-157R

    authors: Schneider C,Nobs SP,Heer AK,Hirsch E,Penninger J,Siggs OM,Kopf M

    更新日期:2017-02-01 00:00:00

  • The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation.

    abstract::Emerging evidence suggests that the innate immune system, comprised of Toll-like receptors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflammation and in the response to invading pathogens. Although TLRs are thought to have predominantly beneficial effects in pathogen r...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1189/jlb.0607358

    authors: Gribar SC,Anand RJ,Sodhi CP,Hackam DJ

    更新日期:2008-03-01 00:00:00

  • Jacalin, a lectin that inhibits in vitro HIV-1 infection, induces intracellular calcium increase via CD4 in cells lacking the CD3/TcR complex.

    abstract::The lectin jacalin interacts with the CD4 cell surface antigen; this lectin inhibits in vitro infection by human immunodeficiency virus type 1 without preventing virus binding on the host cell. The infection process is known to involve cellular events triggered by the binding of the viral external glycoprotein gp120 t...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.56.4.521

    authors: Lafont V,Dornand J,d'Angeac AD,Monier S,Alcover A,Favero J

    更新日期:1994-10-01 00:00:00

  • Intravital imaging of eosinophils: Unwrapping the enigma.

    abstract::Eosinophils are traditionally associated with allergic and parasitic inflammation. More recently, eosinophils have also been shown to have roles in diverse processes including development, intestinal health, thymic selection, and B-cell survival with the majority of these insights being derived from murine models and ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.3HR0220-396R

    authors: Nguyen WNT,Jacobsen EA,Finney CAM,Colarusso P,Patel KD

    更新日期:2020-07-01 00:00:00

  • In vitro assessment of chemokine receptor-ligand interactions mediating mouse eosinophil migration.

    abstract::Eosinophil migration from circulation is controlled, in part, by chemokines through a family of G-protein-coupled chemokine receptors (CCR). Studies of human eosinophils have demonstrated that signaling through CCR3 receptors is a prominent pathway leading to chemotaxis, although several other receptor-ligand interact...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Borchers MT,Ansay T,DeSalle R,Daugherty BL,Shen H,Metzger M,Lee NA,Lee JJ

    更新日期:2002-06-01 00:00:00

  • Role of initial protein phosphorylation events and localized release-activated calcium influx in B cell antigen receptor signaling.

    abstract::An increase in intracellular calcium concentration is one of the major initial steps in B cell activation following antigen receptor (BCR) ligation. We show herein that in C57BL/6 murine B lymphocytes and in model cell lines, BCR-mediated calcium ion (Ca(2+)) influx occurs via highly selective Ca(2+) release-activated...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0308193

    authors: Lyubchenko T,Nielsen JP,Miller SM,Liubchenko GA,Holers VM

    更新日期:2009-02-01 00:00:00