Neutrophils self-limit swarming to contain bacterial growth in vivo

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.

A Multi-Modal Toolkit for Studying Neutrophils in Cancer and Beyond

“…As noted above, the function of neutrophils in vivo is inherently linked to their ability to traffic from the blood into tissues and migrate within tissues to localize their assault at the appropriate site. Not only is there critical spatial regulation at the initiation of neutrophil responses, but recent evidence has even demonstrated that ongoing neutrophil accumulation at sites of inflammation is a self-regulating process based on the spatiotemporal organization of cell swarming in tissues [ 87 ]. Therefore, studying neutrophil responses in tissues using conventional single-cell techniques that ignore spatial architecture (due to the requirement to dissociate tissues into single-cell suspensions) may lead researchers to miss important information about how neutrophils function in vivo.…”

Macrophage network dynamics depend on haptokinesis for optimal local surveillance

“…The ear was immobilized with a strip of Hansaplast tape, which was lightly stretched over the ear and the imaging platform. 2P-IVM was performed using a LSM 780 NLO microscope (Zeiss) enclosed in a custom-built environmental chamber that was maintained at 32°C using heated air (Kienle et al, 2021). Anesthetized mice were kept in the heated environmental chamber for 15 to 30 min until the ear tissue had settled.…”

Neutrophil swarm control: what goes up must come down

“…All biological systems rely on regulatory networks of positive and negative feedback that enable targeted and rapid adaptations, while negative autosignals limit overstimulation and enable self-shutdown. A recent publication in Science 1 demonstrates a shutdown mechanism in neutrophils that limits their aggregation dynamics while enhancing bacterial killing. 1 …”

“…A recent publication in Science 1 demonstrates a shutdown mechanism in neutrophils that limits their aggregation dynamics while enhancing bacterial killing. 1 …”

“…The latter mediates the coordinated extravascular aggregation dynamics known as swarming behavior. Kienle et al 1 now show that preprogrammed desensitization of the very G-protein-coupled receptors (GPCRs) that drive swarming is an intrinsic feedback control that leads to dynamic arrest (e). This arrest ensures stable cluster formation and is critical for their antibacterial effector functions.…”