Host-pathogen interaction between macrophage co-cultures with Staphylococcus aureus biofilms

The ability of Staphylococcus aureus to form biofilms is an important virulence factor. During the infectious process, the interaction between biofilms and immune cells is determinant; however, the properties that make biofilms resistant to the immune system are not well characterized. In order to better understand this, we evaluated the in vitro interaction of macrophages during the early stages of S. aureus biofilm formation. Biofilm formation was evaluated by crystal violet staining, light microscopy, and confocal scanning laser microscopy. Furthermore, different activation on L-arginine pathways such as nitric oxide (NO^•) release and the arginase, the production of reactive oxygen species (ROS), the total oxidative stress response (OSR), and levels of cytokine liberation, were determined. Our findings show that the interaction between biofilms and macrophages results in stimuli for catabolism of L-arginine via arginase, but not for NO^•, an increase of ROS production, and activation of the non-enzymatic OSR. We also observed the production of IL-6, but not of TNFα o IL-10 in these co-cultures. These results contribute to a better understanding of host-pathogen interactions and suggest that biofilms increase resistance against immune cell mechanisms, a phenomenon that could contribute to the ability of S. aureus biofilms to establish mature biofilms.