Summary

Fever is an evolutionary conserved response able to stimulate and boost both innate and adaptive immunity. It modifies the normal physiological condition of the body by changing gene-expression patterns and diverse signaling cascades of many cell types. Neutrophils are of the first sentinels of the immune system, specialized cells that are enriched in infection sites under febrile conditions. Temperature dependent recruitment is activated through parallel pathways, such as an increase in both the pool of circulating neutrophils and in the chemoattractant cues produced in the infection sites. Despite the growing understanding of these complex networks, the contribution of heat on the migration dynamics of neutrophils across tissues has remained unknown. Here we report that, in 3D complex environments without any guiding cue, neutrophil-like cells increase their migratory speed and directional persistence at increasing physiologically relevant temperatures. Remarkably, we further show that this response towards heat is an instantaneous Ca2+ independent response that can occur at the single cell level, with a maintained effect over time. These findings support the idea that the ability of fever to boost immunity can be partially driven by a physical and non-genetic response, working independently but in synergy with complex pathophysiological networks.