PMID- 12244198
OWN - NLM
STAT- MEDLINE
DCOM- 20021112
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 169
IP  - 7
DP  - 2002 Oct 1
TI  - Cellular activation, phagocytosis, and bactericidal activity against group B 
      streptococcus involve parallel myeloid differentiation factor 88-dependent and 
      independent signaling pathways.
PG  - 3970-7
AB  - Group B streptococci (GBS) vigorously activate inflammatory responses. We 
      reported previously that a secreted GBS "factor" activates phagocytes via 
      Toll-like receptor (TLR)2 and TLR6, but that GBS cell walls activate cells 
      independently of these receptors. We hypothesized that the phagocytic immune 
      functions in response to GBS, such as inflammation, uptake, and elimination of 
      bacteria, occur through a coordinated engagement of TLRs, along with the 
      coreceptors CD14 and CD11b/CD18. Using various knockout mice we show that 
      GBS-induced activation of p38 and NF-kappaB depends upon the expression of the 
      cytoplasmic TLR adapter protein, myeloid differentiation factor 88 (MyD88), but 
      not TLR2 and/or TLR4. Macrophages with deletions of CD14 and complement receptor 
      3 had a normal cytokine response to whole bacteria, although the response to GBS 
      factor was abrogated in CD14-null cells. The intracellular formation of 
      bactericidal oxygen species proved to be MyD88 dependent; however, uptake of GBS, 
      a prerequisite for intracellular killing by O(2) radicals, occurred independently 
      of MyD88. While deletion of complement receptor 3 greatly diminished the uptake 
      of opsonized GBS, it did not affect the formation of bactericidal O(2) radicals 
      or inflammatory signaling intermediates. We conclude that the inflammatory, 
      bactericidal, and phagocytic responses to GBS occur via parallel but independent 
      processes.
FAU - Henneke, Philipp
AU  - Henneke P
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 
      01605, USA.
FAU - Takeuchi, Osamu
AU  - Takeuchi O
FAU - Malley, Richard
AU  - Malley R
FAU - Lien, Egil
AU  - Lien E
FAU - Ingalls, Robin R
AU  - Ingalls RR
FAU - Freeman, Mason W
AU  - Freeman MW
FAU - Mayadas, Tanya
AU  - Mayadas T
FAU - Nizet, Victor
AU  - Nizet V
FAU - Akira, Shizuo
AU  - Akira S
FAU - Kasper, Dennis L
AU  - Kasper DL
FAU - Golenbock, Douglas T
AU  - Golenbock DT
LA  - eng
GR  - AI23339/AI/NIAID NIH HHS/United States
GR  - AI38515/AI/NIAID NIH HHS/United States
GR  - AI46613/AI/NIAID NIH HHS/United States
GR  - AI52455/AI/NIAID NIH HHS/United States
GR  - DK50305/DK/NIDDK NIH HHS/United States
GR  - GM54060/GM/NIGMS NIH HHS/United States
GR  - HL36028/HL/NHLBI NIH HHS/United States
GR  - RR14466/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CD11b Antigen)
RN  - 0 (CD18 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Differentiation/biosynthesis/genetics/*physiology
MH  - CD11b Antigen/biosynthesis/genetics
MH  - CD18 Antigens/biosynthesis/genetics
MH  - CHO Cells
MH  - Cells, Cultured
MH  - Cricetinae
MH  - DNA-Binding Proteins/biosynthesis/deficiency/genetics
MH  - *Drosophila Proteins
MH  - Humans
MH  - Intracellular Fluid/metabolism/microbiology
MH  - Lipopolysaccharide Receptors/biosynthesis/genetics
MH  - Macrophage Activation/genetics/*immunology
MH  - Macrophages, Peritoneal/*immunology/metabolism/*microbiology
MH  - Membrane Glycoproteins/biosynthesis/deficiency/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88
MH  - NF-kappa B/biosynthesis/metabolism
MH  - Phagocytosis/genetics/*immunology
MH  - Reactive Oxygen Species/*toxicity
MH  - Receptors, Cell Surface/biosynthesis/deficiency/genetics
MH  - Receptors, Immunologic/biosynthesis/deficiency/genetics/*physiology
MH  - Signal Transduction/genetics/*immunology
MH  - Streptococcus agalactiae/growth & development/*immunology
MH  - Streptococcus pneumoniae/immunology
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptor 9
MH  - Toll-Like Receptors
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2002/09/24 06:00
MHDA- 2002/11/26 04:00
CRDT- 2002/09/24 06:00
PHST- 2002/09/24 06:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/09/24 06:00 [entrez]
AID - 10.4049/jimmunol.169.7.3970 [doi]
PST - ppublish
SO  - J Immunol. 2002 Oct 1;169(7):3970-7. doi: 10.4049/jimmunol.169.7.3970.