The requirement for killed Leishmania antigen is unexpected. We hypothesize that cellular pattern recognition receptors synergize with FccRs to either influence signaling pathways and/ or endosome trafficking patterns to target established parasitophorous vacuoles for NADPH oxidase assembly and activation. There are many examples of PRR synergism that can influence the macrophage response and this is a growing area of research. Gallo et. al. previously characterized how antibody concentration during opsonization can influence the macrophage response, with higher concentrations of antibodies promoting an immunoregulatory response that produces increasing levels of IL10. Less is known of the immunomodulatory properties of ICs, although their involvement in inflammation is clear from their ability to promote the Arthus reaction and autoimmunity. A role for ICs in promoting a pro-inflammatory response during infection with intracellular pathogens is relatively unexplored. Studies by Pfefferkorn et. al. demonstrated that soluble ICs can lead to sustained superoxide production. Soluble ICs isolated from Leishmania donovani-infected patients have been shown to modulate macrophage responses in vitro with a significant increase in GM-CSF production. Not surprisingly, the context of the soluble IC/macrophage interaction is important, as some studies using ICs have demonstrated IL-10dependent immunoregulation. As recently discussed by Casadevall and Pirofski the plasticity of the antibody response makes it difficult to definitively demonstrate a positive role for antibodies during intracellular infections. Again, we would suggest that during effective immunity LEE011 molecular weight against intracellular pathogens the B cell response is not just a bystander component, but actively supports the ability of the host to maintain low pathogen loads. The absolute requirement for this B cell response will vary both with the pathogen and the host. In particular, these results suggest that therapies targeting the macrophage response against intracellular pathogens could be pursued through FcR pathways without having to identify pathogen specific epitopes. This pathway may be particularly relevant to situations where the B cell response is unable to generate effective antibodies. Together the data from our in vitro analysis of cross-protection has uncovered a mechanism of macrophage activation effective against the intracellular parasite L. amazonensis that is partially dependent upon antibodies and which is functional post-infection. As in many other bacterial pathogens, the evolution of E. coli towards pathogenic phenotypes has been determined mainly by two mechanisms: the acquisition of virulence genes and the loss or modification of genes of the core genome. E. coli acquires virulence determinants by horizontal gene transfer as parts of plasmids, bacteriophages, transposons or pathogencity islands, and this process plays a crucial role.