Mitochondria-derived vesicles deliver antimicrobial payload to control phagosomal bacteria

Abstract

Pathogenic bacteria taken up into the macrophage phagosome are the target of many anti-microbial effector molecules. Although mitochondria-derived antimicrobial effectors such as reactive oxygen species (mROS) are reported to aid in bacterial killing, it is unclear how these effectors reach bacteria within the phagosomal lumen. To examine the crosstalk between mitochondria and phagosomes, we monitored the production and the spatial localization of mROS during methicillin-resistant Staphylococcus aureus (MRSA) infection. We showed here mROS, specifically hydrogen peroxide (mH2O2) can be delivered into phagosomes via infection-induced mitochondria-derived vesicles, which are generated in a Parkin-dependent manner. Accumulation of mH2O2 in phagosomes required TLR signaling and the mitochondrial superoxide dismutase, Sod2, which converts superoxide into mH2O2. These data highlight a novel mechanism by which the mitochondrial redox capacity enhances macrophage antimicrobial function by delivering mitochondria-derived effector molecules into bacteria-containing phagosomes.