Mechanisms of interaction of staphylococcus aureus with human mesenchymal stem cells and their differentiated phenotypes

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells commonly derived from the bone marrow, adipose tissue and placenta. Human bone marrow derived MSCs migrate to a site of injury, release proinflammatory cytokines and modulate T-cell proliferation. At sites of injury, MSCs may well encounter bacterial pathogens most commonly the Gram positive pathogen Staphylococcus aureus. However, the precise molecular mechanism(s) of this interaction remain to be elucidated. In the present study we aim to show if a direct interaction occurs between S. aureus and bone marrow derived MSCs and identify if MSCRAMMs have a role in this interaction. We further aim to compare S. aureus interaction with cells that differentiate from MSCs, namely; osteoblasts, adipocytes and chondrocytes, since MSCs co-exist in the niche of these cells. Our results showed that S. aureus is able to interact with MSCs in the form of adhesion and invasion to the cells, and that this interaction is largely dependent on the expression of fibronecting-binding protein (FnBP) by S. aureus. We also showed that the same mechanism of interaction to osteoblasts, adipocytes and chondrocytes that are directly differentiated from the same MSCs. Finally, we have found that the presence of 10% FBS in the infection medium is essential as it helps in achieving the best specific bacterial-cell association with the least background association. The results reveals a mechanism of interaction between S. aureus and MSCs that could pave the way for therapeutic intervention that minimises the burden of infection in inflammatory diseases.