Novel aspects on the role of IFN-beta in inflammation and immunity

The complexity of the IFN system is well known and data generated within this work has added to the complexity, though also initiated studies that will hopefully broaden the understanding of the type I IFN system. Initially, the hierarchy of type I IFNs in fibroblasts was studied. The dominance of IFN-beta for efficient type I IFN expression in fibroblasts after virus infection was confirmed in primary cells. Immortalized fibroblasts had a modified expression pattern of type I IFNs, although type I IFN secreted from these cells remained similar to that of primary cells. This dominance of IFN-beta might be found in other cell types and has implications for how certain cells respond to different stimuli. IFN-beta also influences cell proliferation by delaying initiation of proliferation in a cell density dependent manner in vitro, a finding that could be of importance in vivo, e.g. in tissue regeneration. Type I IFNs can exert both protective and detrimental immunomodulatory effects on the host. Bone marrow derived macrophages and dendritic cells were tested for their T cell stimulatory capacity in vitro, and macrophages exhibited a dependence on IFN-beta while dendritic cells did not. In an in vivo bacterial infection model, in which type I IFNs were previously shown to have detrimental effects on the host, lack of IFN-beta did not ameliorate the effects of the bacterial infection, highlighting that some cell types probably do not require IFN-beta as a master inducer of type I IFNs. Finally, IFN-beta deficient mice were less susceptible to chemically induced inflammatory bowel disease, illustrating a setting in which type I IFN production is detrimental to the host. Taken together, this work highlights the importance of mapping how different cells types involved in immunological reactions react to different stimuli concerning type I IFN induction, as differences in the type I IFN hierarchies might explain the different phenotypes found in different inflammatory models.