Type I interferons, an innate defense classically Butenafine hydrochloride associated with an antiviral NSC 632839 immune state and produced at high levels by plasmacytoid dendritic cells, are now known to be induced in response to a variety of intracellular and extracellular bacterial pathogens. Previously, using an ex vivo coincubation model, we demonstrated that human pDCs and CD11c + CD14 + monocytoid cells produce IFN-a protein following phagocytosis of B. burgdorferi. It has also been shown that IFNa is present at higher levels in the serum of Lyme disease patients with multiple erythema migrans lesions, an indicator of disseminated infection, compared to those of patients with a single EM. The expression of IFN-a in the EM lesion correlates with the presence of monocytoid and plasmacytoid dendritic cells, both of which are enriched approximately 5-fold in the EM lesion infiltrate as compared with the skin of uninfected controls. The interactions of B. burgdorferi with a specific innate immune cell population might facilitate dissemination and promote Lyme disease pathogenesis. The type III IFNs, or IFN-ls, discovered in 2003, are a family of novel cytokines that includes three members: IFN-l1, IFN-l2, and IFN-l3, also known as IL-29, IL-28A, and IL-28B, respectively. 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. Although initially identified as anti-viral proteins, recent studies demonstrate that type III IFNs are an important component of the innate immune r esponse to non-viral pathogens, including Salmonella enterica serovar typhimurium and Listeria monocytogenes. However, the expression pattern of the IFN-l receptor is far more restricted than that of the type I IFN receptor; IFNlR is expressed solely in epithelial tissues and epithelial-like cell types, suggesting that the effects exerted on innate immunity likely are more important for pathogens interacting with the epithelium. Notably, L. monocytogenes pathogenesis is promoted by type I IFNs but can be further enhanced by cooperative interactions between type I IFNs and IL28B.