Bone marrow mesenchymal stem cells offer an immune-privileged niche to Cutibacterium acnes in case of implant-associated osteomyelitis

Considered as some of the most devastating complications, Cutibacterium acnes ( C. acnes)-related os-teomyelitis are among the hardest infections to diagnose and treat. Mesenchymal stem cells (MSCs) se-crete number of immunomodulatory and antimicrobial soluble factors, making them an attractive treat-ment for bacterial infection. In this study, we examined MSCs/C. acnes interaction and analyzed the sub-sequent MSCs and bacteria's behaviors. Human bone marrow-derived MSCs were infected by C. acnes clinical strain harvested from non-infected bone site. Following 3 h of interaction, around 4% of bacte-ria were found in the intracellular compartment. Infected MSCs increased the secretion of prostaglandin E2 and indolamine 2,3 dioxygenase immunomodulatory mediators. Viable intracellular bacteria analyzed by infrared spectroscopy and atomic force microscopy revealed deep modifications in the wall features. In comparison with unchallenged bacteria, the viable intracellular bacteria showed (i) an increase in biofilm formation on orthopaedical-based materials, (ii) an increase in the invasiveness of osteoblasts and (iii) persistence in macrophage, suggesting the acquisition of virulence factors. Overall, these re-sults showed a direct impact of C. acnes on bone marrow-derived MSCs, suggesting that blocking the C. acnes/MSCs interactions may represent an important new approach to manage chronic osteomyelitis infections. Statement of significance The interaction of bone commensal C. acnes with bone marrow mesenchymal stem cells induces modifica-tions in C. acnes wall characteristics. These bacteria increased (i) the biofilm formation on orthopaedical-based materials, (ii) the invasiveness of bone forming cells and (iii) the resistance to macrophage clear-ance through the modification of the wall nano-features and/or the increase in catalase production. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.