Format

Send to

Choose Destination
Nat Microbiol. 2018 Jun;3(6):708-717. doi: 10.1038/s41564-018-0159-x. Epub 2018 May 7.

Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.

Author information

1
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
2
Department of Microbiology, University of Chicago, Chicago, IL, USA.
3
CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France.
4
Department of Microbiology and Immunology, UCSF Diabetes Center, Keck Center for Noncoding RNA, University of California, San Francisco, San Francisco, CA, USA.
5
Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
6
CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France. thomas.henry@inserm.fr.
7
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. a.n.spaan@umcutrecht.nl.
8
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. a.n.spaan@umcutrecht.nl.

Abstract

The 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.

PMID:
29736038
DOI:
10.1038/s41564-018-0159-x

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center