Show simple item record

dc.contributor.authorTromp, Angelino T
dc.contributor.authorVan Gent, Michiel
dc.contributor.authorAbrial, Pauline
dc.contributor.authorMartin, Amandine
dc.contributor.authorJansen, Joris P
dc.contributor.authorDe Haas, Carla JC
dc.contributor.authorVan Kessel, Kok PM
dc.contributor.authorBardoel, Bart W
dc.contributor.authorKruse, Elisabeth
dc.contributor.authorBourdonnay, Emilie
dc.contributor.authorBoettcher, Michael
dc.contributor.authorMcManus, Michael T
dc.contributor.authorDay, Christopher J
dc.contributor.authorJennings, Michael P
dc.contributor.authorLina, Gerard
dc.contributor.authorVandenesch, Francois
dc.contributor.authorVan Strijp, Jos AG
dc.contributor.authorLebbink, Robert Jan
dc.contributor.authorHaas, Pieter-Jan A
dc.contributor.authorHenry, Thomas
dc.contributor.authorSpaan, Andras N
dc.date.accessioned2019-06-26T06:03:04Z
dc.date.available2019-06-26T06:03:04Z
dc.date.issued2018
dc.identifier.issn2058-5276
dc.identifier.doi10.1038/s41564-018-0159-x
dc.identifier.urihttp://hdl.handle.net/10072/381653
dc.description.abstractThe staphylococcal bi-component leukocidins Panton–Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins’ S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin’s F-component LukF-PV. By performing a genome-wide CRISPR–Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom708
dc.relation.ispartofpageto717
dc.relation.ispartofjournalNature Microbiology
dc.relation.ispartofvolume3
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchcode060599
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1108
dc.titleHuman CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorJennings, Michael P.
gro.griffith.authorDay, Christopher J.


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record