The aim of this thesis is best described by Sun Tzu, a 6th century B.C. Chinese general. In his book ‘The Art of War’ he wrote “If you know both yourself and your enemy, you can win numerous battles without jeopardy”. This also holds true for battling bacterial infections. This thesis describes our efforts in exploring the interactions between the host neutrophil and the enemy bacteria. In chapter 2, we characterized LILRs as potent modulators of FcγR-mediated effector functions of neutrophils, including ROS production, phagocytosis and killing of microbes. In chapter 3, we set out a high-throughput screening method, the secretome phage display, to discover novel S. aureus immune interaction proteins targeting human neutrophils. We identified and characterized the staphylococcus superantigen like protein 13 (SSL13), which acts as a neutrophil activator via human FPR2. In chapter 4, using the same screening method as chapter 3, we identified and characterized a new immunoglobulin binding protein from the gut microbiome. In chapter 5, we exploit CHIPS as a potential candidate to treat C5aR mediated diseases in humans. Finally, we discuss the role of these new identified immune interaction proteins and the role of diverse neutrophil receptors, as well as their therapeutic implications in Chapter 6.