Mitochondrial Transfer to Granulocytic Myeloid-Derived Suppressor Cells Augments Immunosuppressive Activity

Authors

• Prabhakar Arumugam, University of Nebraska Medical CenterFollow
• Cortney E. Heim, University of Nebraska Medical Center
• Rachel W. Fallet, University of Nebraska Medical CenterFollow
• Dhananjay Shinde, University of Nebraska Medical CenterFollow
• Vinai Chittezham Thomas, University of Nebraska Medical CenterFollow
• Rafael J. Argüello, Aix-Marseille University
• Tammy Kielian, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Cell Reports

Publication Date

2026

Volume

45

Abstract

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 shaped not only by S. aureus products but also by intrinsic metabolic programs. This study explores whether G-MDSC activity can be modulated by increasing mitochondrial abundance using a co-culture paradigm with macrophages as a mitochondrial donor. Macrophages transfer mitochondria directly to G-MDSCs via tunneling nanotubes, enhancing G-MDSC respiration, as reflected by increased basal, maximal, and spare respiratory capacity. Augmenting mitochondrial abundance in G-MDSCs enhances T cell-suppressive activity and reduces tumor necrosis factor (TNF) and interleukin 6 (IL-6) production. In a mouse model of S. aureus prosthetic joint infection, adoptively transferred macrophages deliver mitochondria to G-MDSCs, enhancing their suppressive activity and increasing bacterial burden, which is reversed when macrophages with non-functional mitochondria are introduced. These findings support the theory that G-MDSCs exploit mitochondria to augment their anti-inflammatory properties in response to S. aureus biofilm.

MeSH Headings

Animals, Myeloid-Derived Suppressor Cells, Mitochondria, Staphylococcus aureus, Mice, Macrophages, Granulocytes, Mice, Inbred C57BL, Staphylococcal Infections, Biofilms, Coculture Techniques, Tumor Necrosis Factor-alpha

DOI Link

10.1016/j.celrep.2026.117057

ISSN

2211-1247

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Arumugam, Prabhakar; Heim, Cortney E.; Fallet, Rachel W.; Shinde, Dhananjay; Chittezham Thomas, Vinai; Argüello, Rafael J.; and Kielian, Tammy, "Mitochondrial Transfer to Granulocytic Myeloid-Derived Suppressor Cells Augments Immunosuppressive Activity" (2026). Journal Articles: Pathology and Microbiology. 123.
https://digitalcommons.unmc.edu/com_pathmicro_articles/123