PMID- 17085599
OWN - NLM
STAT- MEDLINE
DCOM- 20070105
LR  - 20181201
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 103
IP  - 46
DP  - 2006 Nov 14
TI  - Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells.
PG  - 17343-8
AB  - Dendritic cells (DCs) express multiple Toll-like receptors (TLR) in distinct 
      cellular locations. Herpes simplex viruses (HSV) have been reported to engage 
      both the surface TLR2 and intracellular TLR9 in conventional DCs. However, the 
      contributions of these TLRs in recognition of HSV and the induction of 
      proinflammatory cytokines in DCs remain unclear. Here, we demonstrate that a rare 
      population of HSV, both in laboratory strains and in primary clinical isolates 
      from humans, has the capacity to activate TLR2. This virus population is 
      recognized through both TLR2 and TLR9 for the induction of IL-6 and IL-12 
      secretion from bone marrow-derived DCs. Further, we describe a previously 
      uncharacterized pathway of viral recognition in which TLR2 and TLR9 are engaged 
      in sequence within the same DC. Live viral infection results in two additional 
      agonists of TLR2 and TLR9. These results indicate that in cells that express 
      multiple TLRs, pathogens that contain multiple pathogen-associated molecular 
      patterns can be detected in an orchestrated sequence and suggest that the innate 
      immune system in DCs is optimized to linking uptake and degradation of pathogens 
      to microbial recognition.
FAU - Sato, Ayuko
AU  - Sato A
AD  - Section of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Linehan, Melissa M
AU  - Linehan MM
FAU - Iwasaki, Akiko
AU  - Iwasaki A
LA  - eng
GR  - R01 AI054359/AI/NIAID NIH HHS/United States
GR  - R01 AI064705/AI/NIAID NIH HHS/United States
GR  - AI054359/AI/NIAID NIH HHS/United States
GR  - AI064705/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061103
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Genetic Variation/genetics
MH  - Humans
MH  - Lipopolysaccharide Receptors/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Simplexvirus/classification/genetics/*immunology/isolation & purification
MH  - Toll-Like Receptor 2/deficiency/genetics/*immunology/metabolism
MH  - Toll-Like Receptor 9/deficiency/genetics/*immunology/metabolism
PMC - PMC1859932
COIS- The authors declare no conflict of interest.
EDAT- 2006/11/07 09:00
MHDA- 2007/01/06 09:00
PMCR- 2007/05/14
CRDT- 2006/11/07 09:00
PHST- 2006/11/07 09:00 [pubmed]
PHST- 2007/01/06 09:00 [medline]
PHST- 2006/11/07 09:00 [entrez]
PHST- 2007/05/14 00:00 [pmc-release]
AID - 0605102103 [pii]
AID - 4093 [pii]
AID - 10.1073/pnas.0605102103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17343-8. doi: 
      10.1073/pnas.0605102103. Epub 2006 Nov 3.