Type I interferons in infectious disease

Abstract

Type I interferons (IFNs) have diverse effects on innate and adaptive immune cells during infection with viruses, bacteria, parasites and fungi, directly and/or through the induction of other mediators. Type I IFNs are important for host defence against viruses. However, more recently, they have been shown to cause immune pathology in some acute viral infections, such as influenza virus, and, conversely, they can lead to immune suppression during chronic viral infections, such as lymphocytic choriomeningitis virus. During bacterial infections, type I IFNs may be required early and at low levels to initiate cell-mediated immune responses. High concentrations of type I IFNs may block B cell responses or lead to the production of immunosuppressive molecules and also reduce the responsiveness of macrophages to activation by IFN _γ, as shown for infections with Listeria monocytogenes and Mycobacterium tuberculosis. Recent studies in experimental models of tuberculosis have demonstrated that prostaglandin E2 and interleukin-1 inhibit type I IFN expression and the downstream effects, demonstrating the cross-regulatory network of cytokines that operates during infectious diseases to provide protection with minimum host damage.