Innate host defence depends on efficient phagocytosis that is mainly mediated by polymorphonuclear neutrophils (PMN). Phagocytosis is facilitated upon opsonization of bacteria by the complement factor iC3b which is recognized by the b2 integrin CD11b/CD18. Here, we studied the functional impact of CD11b/CD18-mediated signaling for phagocytosis of iC3b- opsonized E. coli. By means of confocal microscopy, we found that binding iC3b-opsonized E. coli to CD11b/CD18 induced the formation of a signalosome consisting of the tyrosine kinase Syk, the actin binding protein Hip-55, and the large GTPase dynamin. This effect was abolished upon pharmacological inhibition of Syk using piceatannol (30 mM). Pharmacological inhibition of Syk or downregulation of Syk by shRNA technique significantly inhibited phagocytosis of iC3b-opsonized E. coli to 41.6%± 2.5 % and 24.8%± 18.7 (p < 0.005) when compared to phagocytosis of untreated control cells (100%). Similar results were obtained using murine Syk deficient PMN, where phagocytosis was reduced to 31.2 ± 18.5 (p < 0.005). In addition, downregulation of Hip-55 by shRNA significantly impaired phagocytosis to 46.4%± 26.5% (p < 0.005). In conclusion, our data indicate that signaling via Syk and Hip-55 is required for efficient phagocytosis of iC3b- opsonized bacteria. (Supported by DFG WA 1048/2-3).