Neutrophils use selective autophagy receptor Sqstm1/p62 to targetStaphylococcus aureusfor degradationin vivoin zebrafish

Macroautophagy/autophagy functions to degrade cellular components and intracellular pathogens. Autophagy receptors, including SQSTM1/p62, target intracellular pathogens.Staphylococcus aureusis a significant pathogen of humans, especially in immunocompromise.S. aureusmay use neutrophils as a proliferative niche, but their intracellular fate following phagocytosis has not been analyzedin vivo. In vitro, SQSTM1 can colocalize with intracellularStaphylococcus aureus, but whether SQSTM1 is beneficial or detrimental in host defense againstS. aureus in vivois unknown. Here we determine the fate and location ofS. aureuswithin neutrophils throughout zebrafish infection. We show Lc3 and Sqstm1 recruitment to phagocytosedS. aureusis altered depending on the bacterial location within the neutrophil and that Lc3 marking of bacterial phagosomes within neutrophils may precede bacterial degradation. Finally, we show Sqstm1 is important for controlling cytosolic bacteria, demonstrating for the first time a key role of Sqstm1 in autophagic control ofS. aureusin neutrophils.

Automated summary

This study reveals the fate and location of Staphylococcus aureus within neutrophils, showing that recruitment of Lc3 and Sqstm1 to phagocytosed bacteria depends on bacterial location. Additionally, it demonstrates the key role of Sqstm1 in controlling cytosolic bacteria.