Neutrophils use selective autophagy receptor p62 to target Staphylococcus aureus for degradation in the zebrafish model

Abstract

Autophagy leads to degradation of cellular components and has an important role in restricting intracellular pathogens. Autophagy receptors, including p62, target invading intracellular pathogens to the autophagy pathway for degradation. Staphylococcus aureus is a significant pathogen of humans and often life-threatening in the immunocompromised. Increasing evidence demonstrates that S. aureus is an intracellular pathogen of immune cells and may use neutrophils as proliferative niche but the intracellular fate of S. aureus following phagocytosis by neutrophils has not previously been analysed in vivo. In vitro, p62 is able to co-localise with intracellular Staphylococcus aureus, but whether p62 is beneficial or detrimental in host defence against S. aureus in vivo had not been determined. Here we use zebrafish to determine the fate and location of S. aureus within neutrophils throughout infection. We show that Lc3 and p62 recruitment to phagocytosed S. aureus is altered depending on the bacterial location within the neutrophil. We also show rapid Lc3 marking of bacterial phagosomes within neutrophils which may be associated with subsequent bacterial degradation. Finally, we find that p62 is important for controlling cytosolic bacteria demonstrating for the first time a key role of p62 in autophagic control of S. aureus in neutrophils.