PMID- 21561248
OWN - NLM
STAT- MEDLINE
DCOM- 20120117
LR  - 20211020
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 22
IP  - 9
DP  - 2011 Sep
TI  - NOD2 signaling contributes to the innate immune response against helper-dependent 
      adenovirus vectors independently of MyD88 in vivo.
PG  - 1071-82
LID - 10.1089/hum.2011.002 [doi]
AB  - We previously demonstrated that Toll-like receptor/myeloid differentiation 
      primary response gene 88 (MyD88) signaling is required for maximal innate and 
      acquired [T helper cell type 1 (Th1)] immune responses following systemic 
      administration of helper-dependent adenoviral vectors (HDAds). However, 
      MyD88-deficient mice injected with HDAdLacZ exhibited only partial reduction of 
      innate immune cytokine expression compared with wild-type mice, suggesting 
      MyD88-independent pathways also respond to HDAds. We now show that NOD2, a 
      nucleotide-binding and oligomerization domain (NOD)-like receptor known to detect 
      muramyl dipeptides in bacterial peptidoglycans, also contributes to innate 
      responses to HDAds, but not to humoral or Th1 immune responses. We established 
      NOD2/MyD88 double-deficient mice that, when challenged with HDAds, showed a 
      significant reduction of the innate response compared with mice deficient for 
      either gene singly, suggesting that NOD2 signaling contributes to the innate 
      response independently of MyD88 signaling following systemic administration of 
      HDAds. In addition, NOD2-deficient mice exhibited significantly higher transgene 
      expression than did wild-type mice at an early time point (before development of 
      an acquired response), but not at a later time point (after development of an 
      acquired response). These results indicate that the intracellular sensor NOD2 is 
      required for innate responses to HDAds and can limit transgene expression during 
      early phases of infection.
FAU - Suzuki, Masataka
AU  - Suzuki M
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      TX 77030, USA.
FAU - Cela, Racel
AU  - Cela R
FAU - Bertin, Terry K
AU  - Bertin TK
FAU - Sule, Gautam
AU  - Sule G
FAU - Cerullo, Vincenzo
AU  - Cerullo V
FAU - Rodgers, John R
AU  - Rodgers JR
FAU - Lee, Brendan
AU  - Lee B
LA  - eng
GR  - R00 HL098692/HL/NHLBI NIH HHS/United States
GR  - K99HL098692/HL/NHLBI NIH HHS/United States
GR  - R01HL87836/HL/NHLBI NIH HHS/United States
GR  - R01DK56787/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110708
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adenoviridae/*genetics/*immunology
MH  - Animals
MH  - Epigenomics
MH  - Gene Expression Regulation
MH  - Genetic Vectors/administration & dosage/*immunology
MH  - Helper Viruses/genetics
MH  - *Immunity, Innate/genetics
MH  - Inflammation/immunology
MH  - Liver/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/genetics/*metabolism
MH  - Nod2 Signaling Adaptor Protein/genetics/*metabolism
MH  - RNA, Messenger
MH  - *Signal Transduction
MH  - Transgenes
PMC - PMC3177951
EDAT- 2011/05/13 06:00
MHDA- 2012/01/18 06:00
PMCR- 2012/09/01
CRDT- 2011/05/13 06:00
PHST- 2011/05/13 06:00 [entrez]
PHST- 2011/05/13 06:00 [pubmed]
PHST- 2012/01/18 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - 10.1089/hum.2011.002 [pii]
AID - 10.1089/hum.2011.002 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2011 Sep;22(9):1071-82. doi: 10.1089/hum.2011.002. Epub 2011 Jul 
      8.