Neutrophils self-limit swarming to contain bacterial growth in vivo
Korbinian Kienle, Katharina M. Glaser, Sarah Eickhoff, Michael Mihlan, Konrad Knöpper, Eduardo Reátegui, Maximilian W. Epple, Matthias Gunzer, Ralf Baumeister, Teresa K. Tarrant, Ronald N. Germain, Daniel Irimia, Wolfgang Kastenmüller, Tim Lämmermann
Abstract
Neutrophils communicate with each other to form swarms in infected organs. Coordination of this population response is critical for the elimination of bacteria and fungi. Using transgenic mice, we found that neutrophils have evolved an intrinsic mechanism to self-limit swarming and avoid uncontrolled aggregation during inflammation. G protein-coupled receptor (GPCR) desensitization acts as a negative feedback control to stop migration of neutrophils when they sense high concentrations of self-secreted attractants that initially amplify swarming. Interference with this process allows neutrophils to scan larger tissue areas for microbes. Unexpectedly, this does not benefit bacterial clearance as containment of proliferating bacteria by neutrophil clusters becomes impeded. Our data reveal how autosignaling stops self-organized swarming behavior and how the finely tuned balance of neutrophil chemotaxis and arrest counteracts bacterial escape.