PMID- 16469053
OWN - NLM
STAT- MEDLINE
DCOM- 20060428
LR  - 20061115
IS  - 1462-5814 (Print)
IS  - 1462-5814 (Linking)
VI  - 8
IP  - 3
DP  - 2006 Mar
TI  - Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse 
      classic and non-classic lipopolysaccharides.
PG  - 401-13
AB  - The innate immune system recognizes microbes by characteristic molecules like the 
      Gram-negative lipopolysaccharide (LPS). Lipid A (the LPS bioactive moiety) 
      signals through toll-like receptors (TLRs) to induce pro-inflammatory molecules 
      and small GTPases of the p47 family involved in intracellular pathogen control. 
      We tested TNF-alpha and p47-GTPase induction in macrophages using classical LPSs 
      [lipid As with glucosamine backbones, ester- and amide-linked C14:0(3-OH) and C12 
      to C16 in acyloxyacyl groups] of wild type and mutant Escherichia coli and 
      Yersinia species and non-classical LPSs [lipid As with diaminoglucose, 
      ester-linked 3-OH-fatty acids and C28:0(27-OH) and C23:0(29-OH) in acyloxyacyl 
      groups] of plant endosymbionts (Rhizobium), intracellular pathogens (Brucella and 
      Legionella) and phylogenetically related opportunistic bacteria (Ochrobactrum). 
      Classical but not non-classical LPSs efficiently induced TNF-alpha, IIGP and IGTP 
      p47-GTPase expression. Remarkably, the acyloxyacyl groups in classical LPSs 
      necessary to efficiently induce TNF-alpha were not necessary to induce 
      p47-GTPases, suggesting that different aspects of lipid A are involved in this 
      differential induction. This was confirmed by using PPDM2, a non-endotoxic lipid 
      A-structurally related synthetic glycolipid. Despite their different bioactivity, 
      all types of LPSs signalled through TLR-4 and not through TLR-2. However, whereas 
      TNF-alpha induction was myeloid differentiation factor 88 (MyD88)-dependent, that 
      of p47-GTPases occurred via a MyD88-independent pathway. These observations show 
      that different aspects of the LPS pathogen-associated molecular pattern may be 
      triggering different signalling pathways linked to the same TLR. They also 
      reinforce the hypothesis that non-classical lipid As act as virulence factors by 
      favouring the escape from the innate immune system.
FAU - Lapaque, Nicolas
AU  - Lapaque N
AD  - Centre d'Immunologie INSERM-CNRS-Universite Mediterranee, case 906, 13288 
      Marseille, Cedex 9, France.
FAU - Takeuchi, Osamu
AU  - Takeuchi O
FAU - Corrales, Fernando
AU  - Corrales F
FAU - Akira, Shizuo
AU  - Akira S
FAU - Moriyon, Ignacio
AU  - Moriyon I
FAU - Howard, Jonathan C
AU  - Howard JC
FAU - Gorvel, Jean-Pierre
AU  - Gorvel JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Lipid A)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (O Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (Igtp protein, mouse)
RN  - EC 3.6.1.- (Iigp1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Female
MH  - GTP Phosphohydrolases/*immunology/*metabolism
MH  - Gram-Negative Bacteria/*immunology/metabolism
MH  - Humans
MH  - Lipid A/chemistry/immunology
MH  - Lipopolysaccharides/*chemistry/*immunology
MH  - Macrophages, Peritoneal/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - O Antigens/chemistry/immunology
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2006/02/14 09:00
MHDA- 2006/04/29 09:00
CRDT- 2006/02/14 09:00
PHST- 2006/02/14 09:00 [pubmed]
PHST- 2006/04/29 09:00 [medline]
PHST- 2006/02/14 09:00 [entrez]
AID - CMI629 [pii]
AID - 10.1111/j.1462-5822.2005.00629.x [doi]
PST - ppublish
SO  - Cell Microbiol. 2006 Mar;8(3):401-13. doi: 10.1111/j.1462-5822.2005.00629.x.