PMID- 16988278
OWN - NLM
STAT- MEDLINE
DCOM- 20061128
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 74
IP  - 10
DP  - 2006 Oct
TI  - Escherichia coli prevents phagocytosis-induced death of macrophages via classical 
      NF-kappaB signaling, a link to T-cell activation.
PG  - 5989-6000
AB  - NF-kappaB is a crucial mediator of macrophage inflammatory responses, but its 
      role in the context of pathogen-induced adaptive immune responses has yet to be 
      elucidated. Here, we demonstrate that classical NF-kappaB activation delays 
      phagocytosis-induced cell death (PICD) in Raw 264.7 and bone marrow-derived 
      macrophages (BMDMs) upon ingestion of bacteria from the Escherichia coli 
      laboratory strain Top10. By expression of a nondegradable form of IkappaBalpha 
      (superrepressor) and pyrrolidine dithiocarbamate treatment, prolonged activation 
      of NF-kappaB upon bacterial coculture is suppressed, whereas initial induction is 
      only partially inhibited. This activation pattern results in partial inhibition 
      of cellular activation and reduced expression of costimulatory CD86. Notably, 
      suppression of classical NF-kappaB activation does not influence bacterial uptake 
      rates but is followed by increased production of oxygen radicals and enhanced 
      intracellular killing in Raw macrophages. This is associated with reduced 
      expression of NF-kappaB-dependent antiapoptotic c-IAP-2 and a loss of the 
      mitochondrial transmembrane potential. Accordingly, NF-kappaB inhibition in Raw 
      cells and BMDMs causes increased apoptotic rates within 12 h of bacterial 
      ingestion. Interestingly, accelerated eradication of E. coli in 
      NF-kappaB-inhibited macrophages is associated with reduced antigen-specific 
      T-cell activation in macrophage-lymphocyte cocultures. These data suggest that E. 
      coli inhibits PICD of macrophages via classical, antiapoptotic NF-kappaB 
      activation and thus facilitates signaling to T cells. Subsequently, a proper 
      adaptive immune response is likely to be generated. Conclusively, therapeutic 
      inhibition of classical NF-kappaB activation in macrophages may hamper the 
      initiation of adaptive immunity.
FAU - Groesdonk, Heinrich V
AU  - Groesdonk HV
AD  - Department of Anesthesiology and Intensive Care, University of Ulm, 
      Steinhovelstr. 9, D-89075 Ulm, Germany.
FAU - Schlottmann, Silke
AU  - Schlottmann S
FAU - Richter, Friederike
AU  - Richter F
FAU - Georgieff, Michael
AU  - Georgieff M
FAU - Senftleben, Uwe
AU  - Senftleben U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrrolidines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiocarbamates)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bone Marrow Cells/immunology/microbiology
MH  - Coculture Techniques
MH  - Escherichia coli/*immunology
MH  - I-kappa B Kinase/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphocyte Activation
MH  - Macrophages/drug effects/*immunology/*microbiology
MH  - Mice
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - Phagocytosis/*immunology
MH  - Pyrrolidines/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/*immunology
MH  - Thiocarbamates/pharmacology
PMC - PMC1594883
EDAT- 2006/09/22 09:00
MHDA- 2006/12/09 09:00
PMCR- 2007/02/01
CRDT- 2006/09/22 09:00
PHST- 2006/09/22 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/09/22 09:00 [entrez]
PHST- 2007/02/01 00:00 [pmc-release]
AID - 74/10/5989 [pii]
AID - 0138-06 [pii]
AID - 10.1128/IAI.00138-06 [doi]
PST - ppublish
SO  - Infect Immun. 2006 Oct;74(10):5989-6000. doi: 10.1128/IAI.00138-06.