PMID- 19846880
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 10
DP  - 2009 Nov 15
TI  - Enterobacter sakazakii targets DC-SIGN to induce immunosuppressive responses in 
      dendritic cells by modulating MAPKs.
PG  - 6588-99
LID - 10.4049/jimmunol.0902029 [doi]
AB  - Enterobacter sakazakii (ES) is an emerging pathogen that causes meningitis and 
      necrotizing enterocolitis in infants. Dendritic cells (DCs) are professional 
      phagocytic cells that play an essential role in host defense against invading 
      pathogens; however, the interaction of ES with DCs is not known. In this study, 
      we demonstrate that ES targets DC-specific ICAM nonintegrin (DC-SIGN) to survive 
      in myeloid DCs for which outer membrane protein A (OmpA) expression in ES is 
      critical, although it is not required for uptake. In addition, DC-SIGN expression 
      was sufficient to cause a significant invasion by ES in HeLa cells and intestinal 
      epithelial cells, which are normally not invaded by ES. OmpA(+) ES prevented the 
      maturation of DCs by triggering the production of high levels of IL-10 and 
      TGF-beta and by suppressing the activation of MAPKs. Pretreatment of DCs with Abs 
      to IL-10 and TGF-beta or of bacteria with anti-OmpA Abs significantly enhanced 
      the maturation markers on DCs. Furthermore, DCs pretreated with various 
      inhibitors of MAPKs prohibited the increased production of proinflammatory 
      cytokines stimulated by LPS or OmpA(-) ES. LPS pretreatment followed by OmpA(+) 
      ES infection of DCs failed to induce maturation of DCs, indicating that OmpA(+) 
      ES renders the cells in immunosuppressive state to external stimuli. Similarly, 
      OmpA(+) ES-infected DCs failed to present Ag to T cells as indicated by the 
      inability of T cells to proliferate in MLR. We conclude that ES interacts with 
      DC-SIGN to subvert the host immune responses by disarming MAPK pathway in DCs.
FAU - Mittal, Rahul
AU  - Mittal R
AD  - Division of Infectious Diseases, Childrens Hospital Los Angeles, Los Angeles, CA 
      90027, USA.
FAU - Bulgheresi, Silvia
AU  - Bulgheresi S
FAU - Emami, Claudia
AU  - Emami C
FAU - Prasadarao, Nemani V
AU  - Prasadarao NV
LA  - eng
GR  - R01 AI040567/AI/NIAID NIH HHS/United States
GR  - R01 AI040567-14/AI/NIAID NIH HHS/United States
GR  - R29 AI040567/AI/NIAID NIH HHS/United States
GR  - AI40567/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 - 20091021
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Anthracenes)
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Butadienes)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (U 0126)
RN  - 130068-27-8 (Interleukin-10)
RN  - 149024-69-1 (OMPA outer membrane proteins)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Bacterial Outer Membrane Proteins/genetics/*immunology/metabolism
MH  - Butadienes/pharmacology
MH  - Cell Adhesion Molecules/*immunology/metabolism
MH  - Cell Survival/drug effects/immunology
MH  - Cronobacter sakazakii/*immunology/ultrastructure
MH  - Dendritic Cells/drug effects/*immunology/metabolism/microbiology
MH  - Enterobacteriaceae Infections/*immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/immunology/metabolism/microbiology
MH  - Flavonoids/pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Interleukin-10/immunology/metabolism
MH  - Lectins, C-Type/*immunology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Microscopy, Electron, Scanning
MH  - Microscopy, Electron, Transmission
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & 
      inhibitors/immunology/*metabolism
MH  - Nitriles/pharmacology
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Receptors, Cell Surface/*immunology/metabolism
MH  - Transfection
MH  - Transforming Growth Factor beta/immunology/metabolism
PMC - PMC2796599
MID - NIHMS144598
COIS- DISCLOSURES The authors have no financial conflict of interest.
EDAT- 2009/10/23 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/11/15
CRDT- 2009/10/23 06:00
PHST- 2009/10/23 06:00 [entrez]
PHST- 2009/10/23 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/11/15 00:00 [pmc-release]
AID - jimmunol.0902029 [pii]
AID - 10.4049/jimmunol.0902029 [doi]
PST - ppublish
SO  - J Immunol. 2009 Nov 15;183(10):6588-99. doi: 10.4049/jimmunol.0902029. Epub 2009 
      Oct 21.