Adenovirus phagocytosis by neutrophils triggers a pro-inflammatory response

Adenoviruses are common pathogens that have been engineered and used for medical purposes. While their recognition by innate immune cells such as macrophages and dendritic cells is well characterized, interactions with neutrophils remain poorly understood. Using cytometry,confocal and electron microscopy, we showed that neutrophils bind to antibody-coated adenoviruses and engulf them in a phagosome. Single-cell transcriptomic approach reveals that adenovirus phagocytosis activates a specific transcriptional program in neutrophils. It also triggers calcium entry, reactive oxygen species production in the phagosome and CXCL8 release. Moreover, 4 hours after adenovirus incubation, 50% of neutrophils undergo calcium- and RIPK3-dependent cell death, accompanied by Neutrophil Extracellular Trap emission. This rapid cell death impaired complete viral degradation after 3 hours, allowing residual adenoviruses to retain genomic expression potential in target cells Thus, our data suggest that, during adenoviral infection, the neutrophil response may promote a pro-inflammatory environment that could damage host tissues.