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  • 1
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    CCR5 is a receptor for Staphylococcus aureus leukotoxin ED (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-12-14
    Description: Pore-forming toxins are critical virulence factors for many bacterial pathogens and are central to Staphylococcus aureus-mediated killing of host cells. S. aureus encodes pore-forming bi-component leukotoxins that are toxic towards neutrophils, but also specifically target other immune cells. Despite decades since the first description of staphylococcal leukocidal activity, the host factors responsible for the selectivity of leukotoxins towards different immune cells remain unknown. Here we identify the human immunodeficiency virus (HIV) co-receptor CCR5 as a cellular determinant required for cytotoxic targeting of subsets of myeloid cells and T lymphocytes by the S. aureus leukotoxin ED (LukED). We further demonstrate that LukED-dependent cell killing is blocked by CCR5 receptor antagonists, including the HIV drug maraviroc. Remarkably, CCR5-deficient mice are largely resistant to lethal S. aureus infection, highlighting the importance of CCR5 targeting in S. aureus pathogenesis. Thus, depletion of CCR5(+) leukocytes by LukED suggests a new immune evasion mechanism of S. aureus that can be therapeutically targeted.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536884/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536884/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alonzo, Francis 3rd -- Kozhaya, Lina -- Rawlings, Stephen A -- Reyes-Robles, Tamara -- DuMont, Ashley L -- Myszka, David G -- Landau, Nathaniel R -- Unutmaz, Derya -- Torres, Victor J -- F32 AI098395/AI/NIAID NIH HHS/ -- R01 AI065303/AI/NIAID NIH HHS/ -- R01-AI065303/AI/NIAID NIH HHS/ -- R21 AI087973/AI/NIAID NIH HHS/ -- R21-AI087973/AI/NIAID NIH HHS/ -- R42-MH084372-02A1/MH/NIMH NIH HHS/ -- R56-AI091856-01A1/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jan 3;493(7430):51-5. doi: 10.1038/nature11724. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235831" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Toxins/*metabolism ; CCR5 Receptor Antagonists ; Cell Death ; Cells, Cultured ; Dendritic Cells/cytology/immunology/metabolism ; Exotoxins/*metabolism ; Female ; Humans ; Immune Evasion ; Immunologic Memory ; Jurkat Cells ; Mice ; Myeloid Cells/cytology/immunology/metabolism ; Receptors, CCR5/*metabolism ; Staphylococcus aureus/immunology/*pathogenicity ; T-Lymphocytes/cytology/immunology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Black hole masses, accretion rates and hot- and cold-mode accretion in radio galaxies at z ~ 1 (2014)
    Oxford University Press
    Details
    Publication Date: 2014-12-24
    Description: Understanding the evolution of accretion activity is fundamental to our understanding of how galaxies form and evolve over the history of the Universe. We analyse a complete sample of 27 radio galaxies which includes both high-excitation galaxies (HEGs) and low-excitation galaxies (LEGs), spanning a mnrasrow redshift range of 0.9 〈  z  〈 1.1 and covering a factor of ~1000 in radio luminosity. Using data from the Spitzer Space Telescope combined with ground-based optical and near-infrared imaging, we show that the host galaxies have masses in the range of 10.7 〈 log 10 ( M /M ) 〈 12.0 with HEGs and LEGs exhibiting no difference in their mass distributions. We also find that HEGs accrete at significantly higher rates than LEGs, with the HEG/LEG division lying at an Eddington ratio of  ~ 0.04, which is in excellent agreement with theoretical predictions of where the accretion rate becomes radiatively inefficient, thus supporting the idea of HEGs and LEGs being powered by different modes of accretion. Our study also shows that at least up to L 151 MHz  ~ 3 10 27 W Hz –1 sr –1 , HEGs and LEGs are indistinguishable in terms of their radio properties. From this result we infer that, at least for the lower radio luminosity range, another factor besides accretion rate must play an important role in the process of triggering jet activity.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Black hole masses, accretion rates and hot- and cold-mode accretion in radio galaxies at z ~ 1 (2014)
    Oxford University Press
    Details
    Publication Date: 2014-12-29
    Description: Understanding the evolution of accretion activity is fundamental to our understanding of how galaxies form and evolve over the history of the Universe. We analyse a complete sample of 27 radio galaxies which includes both high-excitation galaxies (HEGs) and low-excitation galaxies (LEGs), spanning a mnrasrow redshift range of 0.9 〈  z  〈 1.1 and covering a factor of ~1000 in radio luminosity. Using data from the Spitzer Space Telescope combined with ground-based optical and near-infrared imaging, we show that the host galaxies have masses in the range of 10.7 〈 log 10 ( M /M ) 〈 12.0 with HEGs and LEGs exhibiting no difference in their mass distributions. We also find that HEGs accrete at significantly higher rates than LEGs, with the HEG/LEG division lying at an Eddington ratio of  ~ 0.04, which is in excellent agreement with theoretical predictions of where the accretion rate becomes radiatively inefficient, thus supporting the idea of HEGs and LEGs being powered by different modes of accretion. Our study also shows that at least up to L 151 MHz  ~ 3 10 27 W Hz –1 sr –1 , HEGs and LEGs are indistinguishable in terms of their radio properties. From this result we infer that, at least for the lower radio luminosity range, another factor besides accretion rate must play an important role in the process of triggering jet activity.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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