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Titel: Pathogen response-like recruitment and activation of neutrophils by sterile immunogenic dying cells drives neutrophil-mediated residual cell killing
VerfasserIn: Garg, Abhishek D.
Vandenberk, Lien
Fang, Shentong
Fasche, Tekele
Van Eygen, Sofie
Maes, Jan
Van Woensel, Matthias
Koks, Carolien
Vanthillo, Niels
Graf, Norbert
de Witte, Peter
Van Gool, Stefaan
Salven, Petri
Agostinis, Patrizia
Sprache: Englisch
Titel: Cell Death and Differentiation
Bandnummer: 24
Heft: 5
Seiten: 832-843
Verlag/Plattform: Springer Nature
Erscheinungsjahr: 2017
Freie Schlagwörter: Acute inflammation
Cell death and immune response
Chemokines
Signal transduction
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Innate immune sensing of dying cells is modulated by several signals. Inflammatory chemokines-guided early recruitment, and pathogen-associated molecular patterns-triggered activation, of major anti-pathogenic innate immune cells like neutrophils distinguishes pathogen-infected stressed/dying cells from sterile dying cells. However, whether certain sterile dying cells stimulate innate immunity by partially mimicking pathogen response-like recruitment/activation of neutrophils remains poorly understood. We reveal that sterile immunogenic dying cancer cells trigger (a cell autonomous) pathogen response-like chemokine (PARC) signature, hallmarked by co-release of CXCL1, CCL2 and CXCL10 (similar to cells infected with bacteria or viruses). This PARC signature recruits preferentially neutrophils as first innate immune responders in vivo (in a cross-species, evolutionarily conserved manner; in mice and zebrafish). Furthermore, key danger signals emanating from these dying cells, that is, surface calreticulin, ATP and nucleic acids stimulate phagocytosis, purinergic receptors and toll-like receptors (TLR) i.e. TLR7/8/9-MyD88 signaling on neutrophil level, respectively. Engagement of purinergic receptors and TLR7/8/9-MyD88 signaling evokes neutrophil activation, which culminates into H2O2 and NO-driven respiratory burst-mediated killing of viable residual cancer cells. Thus sterile immunogenic dying cells perform 'altered-self mimicry' in certain contexts to exploit neutrophils for phagocytic targeting of dead/ dying cancer cells and cytotoxic targeting of residual cancer cells.
DOI der Erstveröffentlichung: 10.1038/cdd.2017.15
URL der Erstveröffentlichung: https://doi.org/10.1038/cdd.2017.15
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-410594
hdl:20.500.11880/36848
http://dx.doi.org/10.22028/D291-41059
ISSN: 1476-5403
1350-9047
Datum des Eintrags: 13-Nov-2023
Bezeichnung des in Beziehung stehenden Objekts: Supplementary information
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1038%2Fcdd.2017.15/MediaObjects/41418_2017_BFcdd201715_MOESM27_ESM.doc
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Pädiatrie
Professur: M - Prof. Dr. Norbert Graf
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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