Abstract The formation of neutrophil extracellular traps (NETs) was recently identified as one of the most important processes for the maintenance of host tissue homeostasis in bacterial infection. Meanwhile, pneumonia infection has a poor effect on cancer patients receiving immunotherapy. Whether pneumonia‐mediated NETs increase lung metastasis remains unclear. In this study, we identified a critical role for multidrug‐resistant Staphylococcus aureus infection‐induced NETs in the regulation of cancer cell metastasis. Notably, S. aureus triggered autophagy‐dependent NETs formation in vitro and in vivo and increased cancer cell metastasis. Targeting autophagy effectively regulated NETs formation, which contributed to the control of cancer metastasis in vivo. Moreover, the degradation of NETs by DNase I significantly suppresses metastasis in lung. Our work offers novel insight into the mechanisms of metastasis induced by bacterial pneumonia and provides a potential therapeutic strategy for pneumonia‐related metastasis.
