A limitation of the study is that several RST2 and RST3 genotypes that have a high likelihood of producing disseminated infection in humans were not analyzed. Similar to type I IFNs, IFN-ls are expressed primarily by monocytes, macrophages and dendritic cells and can be produced by these cells simultaneously with IFN-a and IFN-b. Those results were generated using B. burgdorferi B515, an RST1 clinical isolate that disseminates in mice. In the current study, the cytokine profiles induced SANT-1 clinical isolates of varying genotypes were analyzed using a human PBMC ex vivo co-incubation model. Intriguingly, differential recognition by human dendritic cells was found to be dependent on a highly divergent region of lp36 which is conserved among RST1 isolates. In this study, we used an established human PBMC vivo coincubation model to explore the effect of genotype on the induction of cytokines, including three major classes of IFNs, and to delineate the host cell-pathogen interactions that contribute to the differential induction of IFNs. We observed that RST1 clinical isolates induced significantly higher levels of IFN-a and IFN-l1 than did RST3 clinical isolates. The current investigation was designed to explore the relationship induction of a type I IFN response. Rather than a systematic analysis of all OspC genotypes, the study focused on RST1 genotypes that have a high probability of causing disseminated Estradiol Cypionate infection and RST3 strains with OspC genotypes that have a low probability of causing disseminated infection. Type I and type III IFNs possess overlapping biological activities: both can induce MHC class I antigen expression, regulate transcription of a common subset of interferon-stimulated genes in various cell lines, increase NK and T cell cytotoxicity, promote Th1 responses and mediate cellular apoptosis.