Increasing evidence highlights the importance of the neutrophil response to bacterial infections in the modulation of the pathogenicity of the individual bacterial strains, the concomitant host response, and the course and outcome of infectious diseases. We perform research directed at understanding the signaling pathways that control the molecular mechanisms regulating the neutrophil response to soluble stimuli and particulate stimuli from pathogens during infections. In particular, we have examined the TLR-signaling involved in this regulation, and have dissected the signaling mechanisms that mediate synergism or tolerance during neutrophil activation. In this context, we have identified key roles for IRAK-4 and PI3-kinase but not TRIF during LPS-induced neutrophil activation.