The Yin and Yang of type I interferon activity in bacterial infection

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Abstract
Type I interferons (IFNs), a family of around 20 members, were originally described as antiviral cytokines. Research in recent years has shown that type I IFNs also affect immune responses to bacteria. IFNs are produced in response to bacterial infection when Toll-like receptor 4 (TLR4) or TLR9 are stimulated, or from within the cytoplasm when bacteria enter a cell. Induction of type I IFN genes by bacteria and their products requires activation of IFN regulatory factor 3 (IRF3) and/or IRF7. Most cells in the body must increase the amounts of IRF7 before transcribing the majority of type I IFN genes in response to infection. This occurs through Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signalling by the type I IFN receptor (IFNAR), which is stimulated by low amounts of type I IFNs produced at the onset of infection. Specialized cells known as IFN-producing cells (IPCs) constitutively express IRF7 and immediately produce large amounts of type I IFNs in response to bacterial signals. These cells rapidly activate IRF7 after TLR signalling. Type I IFNs increase immunity to some Gram-negative bacteria by stimulating IFN-γ production. Some studies suggest that type I IFNs inhibit the invasion of epithelial cells and that this activity limits the ability of enteric bacteria to cross the intestinal epithelium. Type I IFNs influence maturation, activation, migration and survival of dendritic cells (DCs). By regulating DC activity, they can indirectly enhance both T cell and B cell-mediated adaptive immunity to bacteria. Type I IFNs exert adverse effects during infection with at least some intracellular bacteria (Listeria monocytogenes and under some circumstances also Mycobacterium tuberculosis). This activity can be attributed to a sensitization of effector cells to bacteria-induced death.