IFNs and STATs in innate immunity to microorganisms

Abstract

Innate immune responses derive from the ability of cells to rapidly combat invading microorganisms without the requirement for an antigen-specific adaptation. These mechanisms have evolved to recognize common microbe-associated molecular patterns and to interfere with conserved replication and survival strategies that support the propagation of microbial invaders. Here, we consider the contributions of one cytokine family, the IFNs, to these innate defense mechanisms. IFNs were first recognized for their ability to impede viral replication, a function that is indeed critical for host survival in response to viral infection. In addition, IFN signaling is now known to play key roles in defending the host from bacteria and other pathogens and to help integrate early, innate responses with later events mediated by the adaptive immune system. The two recognized types of IFN exhibit distinct immunological properties (1). In humans and mice, type I IFNs include a number of IFN-α subtypes and a single species of IFN-β. (The immunological impact of another type I IFN, IFN-ω, is poorly understood and will not be considered here). While type I IFNs can be produced by all cells under appropriate conditions, a subpopulation of immature dendritic cells (DCs) that will be described in more detail below stands out for the extent of its contribution to overall IFN production during infections. IFN-γ is a type II IFN and serves not only to induce antiviral function, but also to activate macrophages, which strengthens innate responses to unicellular microorganisms (2). Unlike the type I IFNs, IFN-γ is produced by a limited number of cell types: activated NK cells, activated Th1 cells, and, in the presence of IL-12 and IL-18, activated DCs and macrophages. Expression of IFN-γ by Th1 cells provides an important link by which the adaptive immune response reinforces macrophage-based innate immunity.