Nature (London), 2013-01, Vol.493 (7430), p.51-55
2013
Details
- Autor(en) / Beteiligte
- Titel
- CCR5 is a receptor for Staphylococcus aureus leukotoxin ED
- Ist Teil von
- Nature (London), 2013-01, Vol.493 (7430), p.51-55
- Ort / Verlag
- London: Nature Publishing Group
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- EBSCOhost Psychology and Behavioral Sciences Collection
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/nature11724Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3536884
- Format
- –
- Schlagworte
- Animals, Bacterial toxins, Bacterial Toxins - metabolism, Bacteriology, Biological and medical sciences, CCR5 Receptor Antagonists, Cell Death, Cells, Cultured, Chemokine receptors, Cytotoxicity, Dendritic Cells - cytology, Dendritic Cells - immunology, Dendritic Cells - metabolism, Exotoxins - metabolism, Female, Fundamental and applied biological sciences. Psychology, HIV, Human immunodeficiency virus, Humans, Immune Evasion, Immunologic Memory, Jurkat Cells, Ligands, Lymphocytes, Mice, Microbiology, Mortality, Myeloid Cells - cytology, Myeloid Cells - immunology, Myeloid Cells - metabolism, Nosocomial infections, Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains, Properties, Receptors, CCR5 - metabolism, Staphylococcus aureus, Staphylococcus aureus - immunology, Staphylococcus aureus - pathogenicity, Staphylococcus infections, T-Lymphocytes - cytology, T-Lymphocytes - immunology, T-Lymphocytes - metabolism, Testing