Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish

Caroline Coombs, Antonios Georgantzoglou, Hazel A. Walker, Julian Patt, Nicole Merten, Hugo Poplimont, Elisabeth M. Busch-Nentwich, Sarah Williams, Christina Kotsi, Evi Kostenis and Milka Sarris ()
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Caroline Coombs: University of Cambridge
Antonios Georgantzoglou: University of Cambridge
Hazel A. Walker: University of Cambridge
Julian Patt: Institute for Pharmaceutical Biology, University of Bonn
Nicole Merten: Institute for Pharmaceutical Biology, University of Bonn
Hugo Poplimont: University of Cambridge
Elisabeth M. Busch-Nentwich: Wellcome Sanger Institute
Sarah Williams: University of Cambridge
Christina Kotsi: University of Cambridge
Evi Kostenis: Institute for Pharmaceutical Biology, University of Bonn
Milka Sarris: University of Cambridge

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract Immune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.

Date: 2019
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DOI: 10.1038/s41467-019-13107-3

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