The Role of IL-15 Signaling in the Induction of Innate Antiviral Responses

Navkiran      Gill; Nicole   M.   Lauzon; Ali   A.   Ashkar

Abstract

Innate immunity plays a critical role against viral infections, acting as the first line of defense against pathogens. Innate antiviral cytokines are induced early in protection and play a vital role in clearance of the infection and survival of the host. Interleukin 15 (IL- 15) is a cytokine that has been implicated in the establishment of an antiviral state. It is part of the 4-alpha helix bundle family, and shares the IL-2Rβ and the common γ chain for signaling. However the 1L-15Rα directs where IL-15 will bind and carry out its functions. IL- 15Rα is present on antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages and assists in their activation yet it is not required on the surface of all APCs. Certain APCs can bind IL-15 through the IL-15Rα and present it in trans to other cells that do not have the alpha receptor. Unlike other cytokines which can act at a distance from the site of secretion, IL-15 is more tightly regulated since cells must both express IL-15Rα and produce IL-15 in order to present it to other cells. IL-15 is one of the only cytokines that preexists in cells and is quickly released after viral infection; hence it is very important in the innate antiviral response. It assists in the initiation of an antiviral state by causing synthesis and secretion of IFNs, release of iNOS and activation, proliferation and differentiation of NK cells. In this review we will focus on IL-15 signaling and the results of this signaling on innate antiviral responses. An understanding of the IL-15 signaling pathway will prove important in the development of novel therapies inducing early innate responses against infections and contributing to overall protection.

Keywords: Innate immunity, IL-15, IFNs, viral infection, NK/NKT cells