PMID- 21339766
OWN - NLM
STAT- MEDLINE
DCOM- 20111206
LR  - 20191210
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 89
IP  - 6
DP  - 2011 Aug
TI  - A critical role for IL-15 in TLR-mediated innate antiviral immunity against 
      genital HSV-2 infection.
PG  - 663-9
LID - 10.1038/icb.2011.7 [doi]
AB  - Innate antiviral immunity, particularly at mucosal surfaces, has a critical role 
      in early control of viral infections. Both type I interferons (IFNs) and 
      interleukin-15 (IL-15) are essential components of innate antiviral immunity. It 
      has been shown that toll-like receptor (TLR) ligand-induced innate antiviral 
      immunity requires IFN-alpha/beta and -lambda receptor signaling. However, it is not known if 
      IL-15 has a role in TLR ligand-mediated antiviral responses. Here, we report that 
      ligands for TLR-3 and TLR-9 cannot confer protection against genital herpes 
      simplex virus-2 (HSV-2) in the absence of IL-15 in vivo. Interestingly, wild-type 
      mice depleted of natural killer (NK) cells and treated with TLR ligands are 
      protected upon HSV-2 challenge, suggesting that the critical role of IL-15 is 
      independent of NK cell-mediated activity. To examine the cytokine response in the 
      absence of IL-15, we investigated TLR ligand-induced IFN-beta and -lambda production in 
      the vaginal washes, but found no impairment in IL-15(-/-) mice. Finally, we 
      report no impairment in the expression of the IFN-stimulated genes in IL-15(-/-) 
      mice. Collectively, the data suggest that TLR ligands induce an IFN-mediated 
      response in the vaginal tract of both wild-type and IL-15(-/-) mice, but its 
      induction is insufficient for providing protection against HSV-2 in the absence 
      of IL-15.
FAU - Thatte, Amit
AU  - Thatte A
AD  - Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, 
      McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
FAU - DeWitte-Orr, Stephanie J
AU  - DeWitte-Orr SJ
FAU - Lichty, Brian
AU  - Lichty B
FAU - Mossman, Karen L
AU  - Mossman KL
FAU - Ashkar, Ali A
AU  - Ashkar AA
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110222
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (CpG phosphorothioate ODN 1826-S)
RN  - 0 (Interleukin-15)
RN  - 0 (Ligands)
RN  - 0 (Toll-Like Receptors)
RN  - 9007-49-2 (DNA)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - Chlorocebus aethiops
MH  - DNA/immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Herpes Genitalis/genetics/*immunology/prevention & control
MH  - Herpesvirus 2, Human/*immunology
MH  - *Immunity, Innate
MH  - Immunity, Mucosal
MH  - Interferons/biosynthesis
MH  - Interleukin-15/genetics/metabolism/*physiology
MH  - Killer Cells, Natural/immunology
MH  - Ligands
MH  - Lymph Nodes/immunology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Toll-Like Receptors/*metabolism
MH  - Vero Cells
EDAT- 2011/02/23 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/02/23 06:00
PHST- 2011/02/23 06:00 [entrez]
PHST- 2011/02/23 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - icb20117 [pii]
AID - 10.1038/icb.2011.7 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2011 Aug;89(6):663-9. doi: 10.1038/icb.2011.7. Epub 2011 Feb 
      22.