Details

Autor(en) / Beteiligte

• Tromp, Angelino T
• Van Gent, Michiel
• Abrial, Pauline
• Martin, Amandine
• Jansen, Joris P
• De Haas, Carla J C
• Van Kessel, Kok P M
• Bardoel, Bart W
• Kruse, Elisabeth
• Bourdonnay, Emilie
• Boettcher, Michael
• McManus, Michael T
• Day, Christopher J
• Jennings, Michael P
• Lina, Gérard
• Vandenesch, François
• Van Strijp, Jos A G
• Lebbink, Robert Jan
• Haas, Pieter-Jan A
• Henry, Thomas
• Spaan, András N

Titel

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

Ist Teil von

• Nature microbiology, 2018-06, Vol.3 (6), p.708-717

Ort / Verlag

England

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (hC5aR1 ) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1 mice. Compared to humans, murine hC5aR1 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 hC5aR1 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.