LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article: Type I Interferons in Bacterial Infections: A Balancing Act.

    Kovarik, Pavel / Castiglia, Virginia / Ivin, Masa / Ebner, Florian

    Frontiers in immunology

    2016  Volume 7, Page(s) 652

    Abstract: Defense against bacterial infections requires activation of the immune response as well as timely reestablishment of tissue and immune homeostasis. Instauration of homeostasis is critical for tissue regeneration, wound healing, and host recovery. Recent ... ...

    Abstract Defense against bacterial infections requires activation of the immune response as well as timely reestablishment of tissue and immune homeostasis. Instauration of homeostasis is critical for tissue regeneration, wound healing, and host recovery. Recent studies revealed that severe infectious diseases frequently result from failures in homeostatic processes rather than from inefficient pathogen eradication. Type I interferons (IFN) appear to play a key role in such processes. Remarkably, the involvement of type I IFNs in the regulation of immune and tissue homeostasis upon bacterial insult may have beneficial or detrimental consequences for the host. The reasons for such ambivalent function of type I IFNs are not understood. The disparate effects of type I IFNs on bacterial infections are in marked contrast to their well-established protective roles in most viral infections. In this review, we will focus on type I IFN effector mechanisms which balance processes involved in immune and tissue homeostasis during specific bacterial infections and highlight the most important missing links in our understanding of type I IFN functions.
    Language English
    Publishing date 2016-12-26
    Publishing country Switzerland
    Document type Review ; Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2016.00652
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.

    Ebner, Florian / Sedlyarov, Vitaly / Tasciyan, Saren / Ivin, Masa / Kratochvill, Franz / Gratz, Nina / Kenner, Lukas / Villunger, Andreas / Sixt, Michael / Kovarik, Pavel

    The Journal of clinical investigation

    2017  Volume 127, Issue 6, Page(s) 2051–2065

    Abstract: Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged ... ...

    Abstract Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection site. In the context of myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment protected mice against lethal soft tissue infection with Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other antiapoptotic B cell leukemia/lymphoma 2 (Bcl2) family members. Higher Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that posttranscriptional gene regulation by TTP schedules the termination of the antimicrobial engagement of neutrophils. The balancing role of TTP comes at the cost of an increased risk of bacterial infections.
    MeSH term(s) Animals ; Apoptosis/immunology ; Cells, Cultured ; Gene Expression Regulation/immunology ; Immunity, Innate ; Mice, Inbred C57BL ; Mice, Transgenic ; Myeloid Cell Leukemia Sequence 1 Protein/genetics ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Neutrophils/immunology ; Neutrophils/metabolism ; Protein Binding ; RNA Stability ; Streptococcal Infections/immunology ; Streptococcal Infections/metabolism ; Streptococcus pyogenes/immunology ; Transcriptome/immunology ; Tristetraprolin/physiology
    Chemical Substances Mcl1 protein, mouse ; Myeloid Cell Leukemia Sequence 1 Protein ; Tristetraprolin ; Zfp36 protein, mouse
    Language English
    Publishing date 2017-05-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI80631
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection.

    Ivin, Masa / Dumigan, Amy / de Vasconcelos, Filipe N / Ebner, Florian / Borroni, Martina / Kavirayani, Anoop / Przybyszewska, Kornelia N / Ingram, Rebecca J / Lienenklaus, Stefan / Kalinke, Ulrich / Stoiber, Dagmar / Bengoechea, Jose A / Kovarik, Pavel

    PLoS pathogens

    2017  Volume 13, Issue 11, Page(s) e1006696

    Abstract: Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost ... ...

    Abstract Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost importance. Here we show that type I interferon (IFN) signaling protects against lung infection with K. pneumoniae by launching bacterial growth-controlling interactions between alveolar macrophages and natural killer (NK) cells. Type I IFNs are important but disparate and incompletely understood regulators of defense against bacterial infections. Type I IFN receptor 1 (Ifnar1)-deficient mice infected with K. pneumoniae failed to activate NK cell-derived IFN-γ production. IFN-γ was required for bactericidal action and the production of the NK cell response-amplifying IL-12 and CXCL10 by alveolar macrophages. Bacterial clearance and NK cell IFN-γ were rescued in Ifnar1-deficient hosts by Ifnar1-proficient NK cells. Consistently, type I IFN signaling in myeloid cells including alveolar macrophages, monocytes and neutrophils was dispensable for host defense and IFN-γ activation. The failure of Ifnar1-deficient hosts to initiate a defense-promoting crosstalk between alveolar macrophages and NK cell was circumvented by administration of exogenous IFN-γ which restored endogenous IFN-γ production and restricted bacterial growth. These data identify NK cell-intrinsic type I IFN signaling as essential driver of K. pneumoniae clearance, and reveal specific targets for future therapeutic exploitations.
    MeSH term(s) Animals ; Drug Resistance, Multiple/immunology ; Interferon Type I/immunology ; Killer Cells, Natural/immunology ; Klebsiella Infections/immunology ; Klebsiella pneumoniae/growth & development ; Klebsiella pneumoniae/immunology ; Macrophages, Alveolar/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor Cross-Talk/immunology ; Respiratory Tract Infections/immunology ; Signal Transduction/immunology
    Chemical Substances Interferon Type I
    Language English
    Publishing date 2017-11-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1006696
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution.

    Sedlyarov, Vitaly / Fallmann, Jörg / Ebner, Florian / Huemer, Jakob / Sneezum, Lucy / Ivin, Masa / Kreiner, Kristina / Tanzer, Andrea / Vogl, Claus / Hofacker, Ivo / Kovarik, Pavel

    Molecular systems biology

    2016  Volume 12, Issue 5, Page(s) 868

    Abstract: Precise regulation of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. However, a global model integrating regulation and functional consequences of inflammation-associated mRNA decay remains to be established. ...

    Abstract Precise regulation of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. However, a global model integrating regulation and functional consequences of inflammation-associated mRNA decay remains to be established. Using time-resolved high-resolution RNA binding analysis of the mRNA-destabilizing protein tristetraprolin (TTP), an inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions in the transcriptome of immunostimulated macrophages. We identify pervasive destabilizing and non-destabilizing TTP binding, including a robust intronic binding, showing that TTP binding is not sufficient for mRNA destabilization. A low degree of flanking RNA structuredness distinguishes occupied from silent binding motifs. By functionally relating TTP binding sites to mRNA stability and levels, we identify a TTP-controlled switch for the transition from inflammatory into the resolution phase of the macrophage immune response. Mapping of binding positions of the mRNA-stabilizing protein HuR reveals little target and functional overlap with TTP, implying a limited co-regulation of inflammatory mRNA decay by these proteins. Our study establishes a functionally annotated and navigable transcriptome-wide atlas (http://ttp-atlas.univie.ac.at) of cis-acting elements controlling mRNA decay in inflammation.
    MeSH term(s) Animals ; Binding Sites ; Cells, Cultured ; Gene Expression Profiling/methods ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Lipopolysaccharides/pharmacology ; Macrophages/drug effects ; Macrophages/immunology ; Mice ; RNA Stability ; RNA, Messenger/chemistry ; RNA, Messenger/metabolism ; Sequence Analysis, RNA ; Tristetraprolin/metabolism
    Chemical Substances Lipopolysaccharides ; RNA, Messenger ; Tristetraprolin
    Language English
    Publishing date 2016-05-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1744-4292
    ISSN (online) 1744-4292
    DOI 10.15252/msb.20156628
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection.

    Ivin, Masa / Dumigan, Amy / de Vasconcelos, Filipe N / Ebner, Florian / Borroni, Martina / Kavirayani, Anoop / Przybyszewska, Kornelia N / Ingram, Rebecca J / Lienenklaus, Stefan / Kalinke, Ulrich / Stoiber, Dagmar / Bengoechea, Jose A / Kovarik, Pavel

    2017  

    Abstract: Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost ... ...

    Abstract Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost importance. Here we show that type I interferon (IFN) signaling protects against lung infection with K. pneumoniae by launching bacterial growth-controlling interactions between alveolar macrophages and natural killer (NK) cells. Type I IFNs are important but disparate and incompletely understood regulators of defense against bacterial infections. Type I IFN receptor 1 (Ifnar1)-deficient mice infected with K. pneumoniae failed to activate NK cell-derived IFN-γ production. IFN-γ was required for bactericidal action and the production of the NK cell response-amplifying IL-12 and CXCL10 by alveolar macrophages. Bacterial clearance and NK cell IFN-γ were rescued in Ifnar1-deficient hosts by Ifnar1-proficient NK cells. Consistently, type I IFN signaling in myeloid cells including alveolar macrophages, monocytes and neutrophils was dispensable for host defense and IFN-γ activation. The failure of Ifnar1-deficient hosts to initiate a defense-promoting crosstalk between alveolar macrophages and NK cell was circumvented by administration of exogenous IFN-γ which restored endogenous IFN-γ production and restricted bacterial growth. These data identify NK cell-intrinsic type I IFN signaling as essential driver of K. pneumoniae clearance, and reveal specific targets for future therapeutic exploitations.
    Keywords Animals ; Drug Resistance ; Multiple ; Interferon Type I ; Killer Cells ; Natural ; Klebsiella Infections ; Klebsiella pneumoniae ; Macrophages ; Alveolar ; Mice ; Inbred C57BL ; Knockout ; Receptor Cross-Talk ; Respiratory Tract Infections ; Signal Transduction
    Subject code 572
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection.

    Ivin, Masa / Dumigan, Amy / de Vasconcelos, Filipe N / Ebner, Florian / Borroni, Martina / Kavirayani, Anoop / Przybyszewska, Kornelia N / Ingram, Rebecca J / Lienenklaus, Stefan / Kalinke, Ulrich / Stoiber, Dagmar / Bengoechea, Jose A / Kovarik, Pavel

    2017  

    Abstract: Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost ... ...

    Abstract Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost importance. Here we show that type I interferon (IFN) signaling protects against lung infection with K. pneumoniae by launching bacterial growth-controlling interactions between alveolar macrophages and natural killer (NK) cells. Type I IFNs are important but disparate and incompletely understood regulators of defense against bacterial infections. Type I IFN receptor 1 (Ifnar1)-deficient mice infected with K. pneumoniae failed to activate NK cell-derived IFN-γ production. IFN-γ was required for bactericidal action and the production of the NK cell response-amplifying IL-12 and CXCL10 by alveolar macrophages. Bacterial clearance and NK cell IFN-γ were rescued in Ifnar1-deficient hosts by Ifnar1-proficient NK cells. Consistently, type I IFN signaling in myeloid cells including alveolar macrophages, monocytes and neutrophils was dispensable for host defense and IFN-γ activation. The failure of Ifnar1-deficient hosts to initiate a defense-promoting crosstalk between alveolar macrophages and NK cell was circumvented by administration of exogenous IFN-γ which restored endogenous IFN-γ production and restricted bacterial growth. These data identify NK cell-intrinsic type I IFN signaling as essential driver of K. pneumoniae clearance, and reveal specific targets for future therapeutic exploitations.
    Keywords Animals ; Drug Resistance ; Multiple ; Interferon Type I ; Killer Cells ; Natural ; Klebsiella Infections ; Klebsiella pneumoniae ; Macrophages ; Alveolar ; Mice ; Inbred C57BL ; Knockout ; Receptor Cross-Talk ; Respiratory Tract Infections ; Signal Transduction
    Subject code 572
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top