On contrast, resistance to

killing can be attributed to PIA as it decreases killing by human PMNs (Vuong et al., 2004). In addition, studies involving planktonic and biofilm phase bacteria showed that biofilm cells are more resistant to opsonic killing than their planktonic counterparts (Cerca et al., 2006), whereas biofilm-embedded wild-type S. epidermidis is killed to a lesser extent by human PMNs (Kristian et al., 2008). We should take into account that most aforementioned studies carried out with PMNs or murine macrophages and with biofilm-producing vs. biofilm nonproducing strains. In this study, experiments were carried out using human macrophages from different donors, and we compared biofilm

this website and planktonic states of the same strain. Biofilms were disrupted only mechanically, without use of ultrasound. The reason for this intervention was that by this way, we were able to use bacterial suspension with the same number of bacterial cells. Our data show that internalization of biofilm phase bacteria does not promote Th1 cytokine production, as the levels of IL-12 and IFN-γ are 5- to 10-fold lower. In contrast, suppressive cytokine IL-13 is Cyclopamine secreted at higher levels upon such stimulation. In our study, biofilm phase bacteria induced higher amounts of GM-CSF as compared to planktonic phase bacteria. Data suggest that GM-CSF can stimulate both Th1 and Th2 type responses (Shi et al., 2006). Biofilm phase bacteria seem to down-regulate proinflammatory cytokine production, such as TNF-α, and this finding is associated

with a more silent course of biofilm-related infections. Internalization of biofilm phase bacteria by human monocytes/macrophages and interaction with lymphocytes induce proinflammatory cytokine release in a variable but adequate extent, whereas adaptive immune responses are down-regulated to higher extent. It seems that upon phagocytosis of biofilm phase bacteria, weaker protective cytokine responses are generated. In accordance with a recent study, a biofilm-negative S. epidermidis strain 1457-M10 induced higher granulocyte activation by expression of CD11b and higher secretion Mannose-binding protein-associated serine protease of cytokines in a human whole-blood ex vivo model than its biofilm-producing isogenic strain 1457, whereas PIA was responsible for stronger complement activation by 1457 strain as compared to its isogenic mutant (Aarag Fredheim et al., 2011). Furthermore, compared to biofilm-negative S. epidermidis strains, isogenic biofilm-forming S. epidermidis induced diminished inflammatory J774A.1 macrophage response, leading to significantly reduced NF-κB activation and IL-1β production (Schommer et al., 2011). Our results indicate that biofilm phase bacteria enhance generation of GM-CSF; this seems to be independent of the activation of NF-κB (Meja et al., 2000). On the contrary, Ciornei et al.