The interplay between staphylococci, biomaterials and host immunity in biomaterial-associated infection

Biomaterial-associated infections (BAIs) are a significant problem associated with implantation of medical devices (biomaterials). Staphylococcus aureus and Staphylococcus epidermidis are the predominant pathogens causing BAI. An important element in the pathogenesis of BAI is derangement of the local immune response compromising clearance of bacteria. The aim of this thesis was to obtain insights in the initiation and regulation of human innate and adaptive immune responses to S. aureus and S. epidermidis in the context of BAI. Therefore, we studied the interactions between human dendritic cells (DCs), S. aureus or S. epidermidis and biomaterials and the ensuing effects on T cells. We showed that S. aureus trigger higher levels of inflammatory DC and T helper (Th) cell responses compared to S. epidermidis. The presence of polymeric biomaterials modulated the inflammatory response of DCs to staphylococci but not the subsequent Th cell response. This research presents an unexplored approach to predict the nature of human adaptive immune responses to the combination of staphylococci and biomaterials in biomaterial-associated infections.
Understanding the route of biomaterial infection and the influence of biomaterial design on bacterial colonization and immune cell function is important to prevent BAI. We observed that the physical design of biomaterials with small pores reduced immune cell infiltration but did not prevent immune cells to reach bacteria within the pores of the biomaterial. Also we identified the skin as a possible source of epidural catheter infection in patients with such catheters. These results provide future directions for the design of anti-infective biomaterials.