PMID- 18684958
OWN - NLM
STAT- MEDLINE
DCOM- 20081006
LR  - 20190516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 4
DP  - 2008 Aug 15
TI  - Outer membrane protein A expression in Escherichia coli K1 is required to prevent 
      the maturation of myeloid dendritic cells and the induction of IL-10 and 
      TGF-beta.
PG  - 2672-82
AB  - Dendritic cells (DCs) are professional APCs that direct both cellular and humoral 
      immune responses. Escherichia coli K1 causes meningitis in neonates; however, the 
      interactions between this pathogen and DCs have not been previously explored. In 
      the present study, we observed that E. coli K1, expressing outer membrane protein 
      A (OmpA), was able to enter, survive, and replicate inside DCs, whereas OmpA(-) 
      E. coli was killed within a short period. Opsonization of OmpA(+) E. coli either 
      with adult or cord serum did not affect its survival inside DCs. Exposure of DCs 
      to live OmpA(+) E. coli K1 prevented DCs from progressing in their maturation 
      process as indicated by failure to up-regulate costimulatory molecules, CD40, 
      HLA-DR, and CD86. The distinct DC phenotype requires direct contact between live 
      bacteria and DCs. The expression of costimulatory molecules was suppressed even 
      after pretreatment of DCs with LPS or peptidoglycan. Furthermore, the suppressive 
      effects of OmpA(+) E. coli on DCs were abrogated when the bacteria were incubated 
      with anti-OmpA Ab. The inhibitory effect on DC maturation was associated with 
      increased production of IL-10 as well as TGF-beta and decreased production of 
      IL-6, TNF-alpha, IL-1beta, and IL-12p70 by DCs, a phenotype associated with 
      tolerogenic DCs. These results suggest that the subversion of DC functions may be 
      a novel strategy deployed by this pathogen to escape immune defense and persist 
      in the infected host to reach a high degree of bacteremia, which is crucial for 
      E. coli to cross the blood-brain barrier.
FAU - Mittal, Rahul
AU  - Mittal R
AD  - Division of Infectious Diseases, Saban Research Institute, Childrens Hospital Los 
      Angeles, Los Angeles, CA 90027, USA.
FAU - Prasadarao, Nemani V
AU  - Prasadarao NV
LA  - eng
GR  - AI40567/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Complement C4b-Binding Protein)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 130068-27-8 (Interleukin-10)
RN  - 149024-69-1 (OMPA outer membrane proteins)
SB  - IM
MH  - Bacterial Outer Membrane Proteins/biosynthesis/blood/genetics/*physiology
MH  - Cell Differentiation/genetics/*immunology
MH  - Cells, Cultured
MH  - Complement C4b-Binding Protein/physiology
MH  - Dendritic Cells/cytology/immunology/metabolism/*microbiology
MH  - Escherichia coli/growth & development/*physiology
MH  - Gene Expression Regulation/immunology
MH  - Growth Inhibitors/*antagonists & inhibitors/biosynthesis/genetics
MH  - Humans
MH  - Interleukin-10/*biosynthesis/genetics
MH  - Myeloid Cells/cytology/immunology/metabolism/*microbiology
MH  - Transforming Growth Factor beta1/*biosynthesis/genetics
EDAT- 2008/08/08 09:00
MHDA- 2008/10/07 09:00
CRDT- 2008/08/08 09:00
PHST- 2008/08/08 09:00 [pubmed]
PHST- 2008/10/07 09:00 [medline]
PHST- 2008/08/08 09:00 [entrez]
AID - 181/4/2672 [pii]
AID - 10.4049/jimmunol.181.4.2672 [doi]
PST - ppublish
SO  - J Immunol. 2008 Aug 15;181(4):2672-82. doi: 10.4049/jimmunol.181.4.2672.