Adaptive immune responses fail to provide protection against genital HSV-2 infection in the absence of IL-15

Publisher Website
Google Scholar
Abstract
IL‐15 plays a crucial role in innate defense against viral infections. The role of IL‐15 in the generation and function of adaptive immunity, following mucosal immunization, against genital HSV‐2 has not been studied. Here, we report that immunized IL‐15–/– mice were able to generate antibody and T cell‐mediated immune responses against HSV‐2, comparable to those seen in immunized B6 mice. However, immunized IL‐15–/– mice were not protected against subsequent HSV‐2 challenge, compared to B6 immunized mice, even with a ten times lower challenge dose. We then examined if the adaptive immune responses generated in the absence of IL‐15 could provide protection against HSV‐2 in an IL‐15‐positive environment. Adoptive transfer of lymphocytes from immunized IL‐15–/– to naive mice were able to provide protection against HSV‐2 challenge similar to protection with immunized cells from control mice. This suggests that the adaptive immune responses raised in the absence of IL‐15 are functional in vivo. Reconstitution of the innate components, particularly IL‐15, NK cells and NK cell‐derived IFN‐γ, in immunized IL‐15–/– mice restored their protective adaptive immunity against subsequent genital HSV‐2 challenge. Our results clearly suggest that innate antiviral activity of IL‐15 is necessary for protective adaptive immunity against genital HSV‐2 infection.