Mitochondrial transfer to granulocytic myeloid-derived suppressor cells augments immunosuppressive activity

The anti-inflammatory properties of granulocytic myeloid-derived suppressor cells (G-MDSCs) promote Staphylococcus aureus (S. aureus) biofilm persistence. Evidence suggests that G-MDSC activity is not only shaped by S. aureus products but also by intrinsic metabolic programs. This study explored whether G-MDSC activity could be modulated by increasing mitochondrial abundance using a co-culture paradigm with macrophages as a mitochondrial donor. Macrophages transferred mitochondria directly to G-MDSCs via tunneling nanotubes, which enhanced G-MDSC respiration as reflected by increased basal, maximal, and spare respiratory capacity. Augmenting mitochondrial abundance in G-MDSCs enhanced T cell suppressive activity concomitant with decreased cytokine production. Adoptive transfer of macrophages in a mouse model of S. aureus prosthetic joint infection revealed mitochondrial transfer to G-MDSCs in vivo that enhanced their suppressive activity, leading to increased bacterial burden. These findings support that G-MDSCs can exploit mitochondria to augment their anti-inflammatory properties in response to S. aureus biofilm.