PMID- 17706458
OWN - NLM
STAT- MEDLINE
DCOM- 20080320
LR  - 20081121
IS  - 1618-0607 (Electronic)
IS  - 1438-4221 (Linking)
VI  - 298
IP  - 1-2
DP  - 2008 Jan
TI  - Structural requirements for uptake and recognition of CpG oligonucleotides.
PG  - 33-8
AB  - Recognition of infectious danger by innate immune cells is a fundamental 
      requirement to directly combat infections and to activate the adaptive immune 
      response of T and B cells. Pathogen-associated molecular patterns (PAMPs) play a 
      fundamental role in this process. PAMPs are sensed by pattern recognition 
      receptors, among which the Toll-like receptors (TLRs) play an important role. 
      Within the TLR ligands, bacterial CpG DNA is peculiar. CpG DNA is recognized by 
      TLR9 and harbors the outstanding propensity to induce a milieu that favors 
      activation of Th1-dominated immune responses. This is mainly due to activation of 
      dendritic cells and subpopulations, thereby inducing an intense interferon and 
      IL-12 response. Therefore, CpG DNA has become a promising candidate for 
      constructing new vaccines as well as for induction of immune responses in cancer 
      and allergy. CpG DNA can be synthesized with high purity, defined base 
      composition and various chemical modifications. We aimed to understand the 
      structural requirements for cellular uptake and activation of CpG DNA, which will 
      improve our means to enhance the intrinsic activity of CpG for therapeutic use. 
      We show that sequence modifications can be utilized to enhance cellular uptake, 
      and that chemical substitutions can confer new qualities to synthetic CpG DNA. 
      Additionally, we propose a model of CpG DNA recognition which occurs by sensing 
      partial duplex forms instead of single-stranded DNA. Moreover, we provide 
      evidence that the propensity of CpG DNA to induce high amounts of IL-12 is due to 
      its unique ability to trigger epigenetic modifications of the IL-12p40 promoter, 
      including acetylation and nucleosomal remodeling. Hence, CpG DNA represents a new 
      and promising class of adjuvant for vaccination.
FAU - Heeg, Klaus
AU  - Heeg K
AD  - Department of Hygiene and Medical Microbiology, Institute of Hygiene, University 
      of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany. 
      klaus.heeg@med.uni-heidelberg.de
FAU - Dalpke, Alexander
AU  - Dalpke A
FAU - Peter, Mirjam
AU  - Peter M
FAU - Zimmermann, Stefan
AU  - Zimmermann S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20070813
PL  - Germany
TA  - Int J Med Microbiol
JT  - International journal of medical microbiology : IJMM
JID - 100898849
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Toll-Like Receptors)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Animals
MH  - Humans
MH  - Immunity, Innate/immunology
MH  - Interferon-gamma/immunology
MH  - Interleukin-12 Subunit p40/immunology
MH  - Oligodeoxyribonucleotides/*immunology
MH  - Structure-Activity Relationship
MH  - Toll-Like Receptors/*immunology
RF  - 29
EDAT- 2007/08/21 09:00
MHDA- 2008/03/21 09:00
CRDT- 2007/08/21 09:00
PHST- 2007/08/21 09:00 [pubmed]
PHST- 2008/03/21 09:00 [medline]
PHST- 2007/08/21 09:00 [entrez]
AID - S1438-4221(07)00102-6 [pii]
AID - 10.1016/j.ijmm.2007.07.007 [doi]
PST - ppublish
SO  - Int J Med Microbiol. 2008 Jan;298(1-2):33-8. doi: 10.1016/j.ijmm.2007.07.007. 
      Epub 2007 Aug 13.