Interleukin-15 and natural killer and NKT cells play a critical role in innate protection against genital herpes simplex virus type 2 infection.
Interleukin-15 (IL-15), natural killer (NK) cells, and NK T (NKT) cells, components of the innate immune system, are known to contribute to defense against pathogens, including viruses. Here we report that IL-15(-/-) (NK(-) and NKT(-/+)) mice and RAG-2(-/-)/gamma(c)(-/-) (NK(-) and NKT(-)) mice that lack all lymphoid cells were very susceptible to vaginal infection with a low dose of herpes simplex virus type 2 (HSV-2). IL-15(-/-) and RAG-2(-/-)/gamma(c)(-/-) mice were 100-fold more susceptible and RAG-2(-/-), CD-1(-/-) (NKT(-)), and gamma interferon (IFN-gamma)(-/-) mice were 10-fold more susceptible to vaginal HSV-2 infection than control C57BL/6 mice. NK and/or NKT cells were the early source of IFN-gamma in vaginal secretions following genital HSV-2 infection. This study demonstrates that IL-15 and NK-NKT cells are critical for innate protection against genital HSV-2.
Ashkar
Ali A
AA
Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Room 4H30G, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. ashkara@mcmaster.ca
Rosenthal
Kenneth L
KL
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D004198:Disease Susceptibility; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000502:physiology; D019409:Interleukin-15 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D014621:Vagina / Q000276:immunology
D004268:DNA-Binding Proteins; D019409:Interleukin-15; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D007371:Interferon-gamma