COMMD10-Guided Phagolysosomal Maturation Promotes Clearance of Staphylococcus Aureus in Macrophages

Staphylococcus aureus (S. aureus) is a major cause of infectious disease. Macrophages, and especially liver Kupffer cells (KCs), are responsible for sequestering and destroying S. aureus bacteria through the phagolysosomal pathway. Proteins belonging to the COMMD family emerge as key intracellular regulators of protein trafficking, but the role of COMMD10 in macrophage-mediated eradication of S. aureus is unknown. Here we report that COMMD10-deficiency in macrophages did not affect S. aureus internalization, but was necessary for its timely elimination, as demonstrated with two different S. aureus subspecies. In vivo, COMMD10-deficient liver KCs exhibited impaired clearance of systemic S. aureus infection. S. aureus-infected COMMD10-deficient macrophages exhibited impaired activation of the transcription factor EB, resulting in reduced lysosomal biogenesis. Moreover, S. aureus-initiated phagolysosomal maturation and function was significantly attenuated in the COMMD10-deficient macrophages. Collectively, these results support an important role for COMMD10 in instructing macrophage phagolysosomal biogenesis and maturation during S. aureus infection.