Neutrophils exert protection in earlyAeromonas veroniiinfections through the clearance of both bacteria and dying macrophages

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Abstract

Aeromonas veronii is a gram-negative opportunistic pathogen capable of infecting both fish and mammals. Left untreated, natural infection in fish can prove fatal and result in irreparable damage to the aquaculture industry. Neutrophils are essential innate effector cells that play critical roles in pathogen defense. Our aim was to investigate the immunological roles of teleost neutrophils during infection with A. veronii. We began by examining the functional defenses of neutrophils in vitro, where neutrophils efficiently killed the pathogen. In addition, we developed an in vivo infection model to assess the roles of neutrophils during an infection in goldfish. This allowed us to explore the complex dynamics between immune cells and Aeromonas veronii. Interestingly, our studies found that neutrophils are capable of sensing a diverse range of dead and dying cells, resulting in varying downstream responses. Herein, we report that neutrophils internalized dead or dying macrophages previously infected with A. veronii. Moreover, once internalized, neutrophils went on to display classical pro-inflammatory ROS responses, in contrast to the more typical anti-inflammatory responses seen in cells following the uptake of a dead host cell. This led us to hypothesize that during infection, neutrophils are capable of simultaneously clearing dead and dying cells as well as A. veronii. This study provides additional insights into the complex mechanisms by which neutrophils operate within an inflammatory site and contribute to the induction and regulation of acute inflammatory responses.

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