PMID- 23907435
OWN - NLM
STAT- MEDLINE
DCOM- 20140107
LR  - 20211203
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 11
DP  - 2013 Nov
TI  - Helminth-excreted/secreted products are recognized by multiple receptors on DCs 
      to block the TLR response and bias Th2 polarization in a cRAF dependent pathway.
PG  - 4547-60
LID - 10.1096/fj.13-228932 [doi]
AB  - Dendritic cells (DCs) recognize pathogens and initiate the T-cell response. The 
      DC-helminth interaction induces an immature phenotype in DCs; as a result, these 
      DCs display impaired responses to TLR stimulation and prime Th2-type responses. 
      However, the DC receptors and intracellular pathways targeted by helminth 
      molecules and their importance in the initiation of the Th2 response are poorly 
      understood. In this report, we found that products excreted/secreted by Taenia 
      crassiceps (TcES) triggered cRAF phosphorylation through MGL, MR, and TLR2. TcES 
      interfered with the LPS-induced NFkappaB p65 and p38 MAPK signaling pathways. In 
      addition, TcES-induced cRAF signaling pathway was critical for down-regulation of 
      the TLR-mediated DC maturation and secretion of IL-12 and TNF-alpha. Finally, we show 
      for the first time that blocking cRAF in DCs abolishes their ability to induce 
      Th2 polarization in vitro after TcES exposure. Our data demonstrate a new 
      mechanism by which helminths target intracellular pathways to block DC maturation 
      and efficiently program Th2 polarization.
FAU - Terrazas, Cesar A
AU  - Terrazas CA
AD  - 1A.S., Department of Pathology, The Ohio State University, Columbus, OH 43210, 
      USA. abhay.satoskar@osumc.edu.
FAU - Alcantara-Hernandez, Marcela
AU  - Alcantara-Hernandez M
FAU - Bonifaz, Laura
AU  - Bonifaz L
FAU - Terrazas, Luis I
AU  - Terrazas LI
FAU - Satoskar, Abhay R
AU  - Satoskar AR
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130801
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Asialoglycoproteins)
RN  - 0 (Clec10a protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Asialoglycoproteins/genetics/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Down-Regulation
MH  - Immunomodulation
MH  - Interleukin-12/metabolism
MH  - Lectins, C-Type/genetics/metabolism
MH  - MAP Kinase Signaling System
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-raf/*metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Taenia/*immunology
MH  - Th2 Cells/*immunology/metabolism
MH  - Toll-Like Receptor 2/*metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3804751
OTO - NOTNLM
OT  - CLRs
OT  - MGL
OT  - dendritic cell
OT  - immunomodulation
OT  - mannose receptor
EDAT- 2013/08/03 06:00
MHDA- 2014/01/08 06:00
PMCR- 2014/11/01
CRDT- 2013/08/03 06:00
PHST- 2013/08/03 06:00 [entrez]
PHST- 2013/08/03 06:00 [pubmed]
PHST- 2014/01/08 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - fj.13-228932 [pii]
AID - 13-228932 [pii]
AID - 10.1096/fj.13-228932 [doi]
PST - ppublish
SO  - FASEB J. 2013 Nov;27(11):4547-60. doi: 10.1096/fj.13-228932. Epub 2013 Aug 1.