Adaptive immune responses fail to provide protection against genital HSV-2 infection in the absence of IL-15.
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-gamma, 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.
Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Navkiran
N
Gill
Ali A
AA
Ashkar
D000220:Adaptation, Biological / Q000276:immunology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000276:immunology*; D007114:Immunization; D019409:Interleukin-15 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D015996:Survival Rate
D000998:Antiviral Agents; D019409:Interleukin-15; D011994:Recombinant Proteins