PMID- 10548109
OWN - NLM
STAT- MEDLINE
DCOM- 19991116
LR  - 20061115
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6755
DP  - 1999 Oct 21
TI  - The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates 
      between pathogens.
PG  - 811-5
AB  - Macrophages orchestrate innate immunity by phagocytosing pathogens and
      coordinating inflammatory responses. Effective defence requires the host to
      discriminate between different pathogens. The specificity of innate immune
      recognition in Drosophila is mediated by the Toll family of receptors; Toll
      mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial
      defence. A large number of Toll homologues have been identified in mammals, and
      Toll-like receptor 4 is critical in responses to Gram-negative bacteria. Here we 
      show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes
      containing yeast, and that a point mutation in the receptor abrogates
      inflammatory responses to yeast and Gram-positive bacteria, but not to
      Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes
      of innate immune receptors cooperate to mediate host defence: phagocytic
      receptors, such as the mannose receptor, signal particle internalization, and the
      Toll-like receptors sample the contents of the vacuole and trigger an
      inflammatory response appropriate to defence against the specific organism.
FAU - Underhill, D M
AU  - Underhill DM
AD  - Department of Immunology, University of Washington, Seattle 98195, USA.
FAU - Ozinsky, A
AU  - Ozinsky A
FAU - Hajjar, A M
AU  - Hajjar AM
FAU - Stevens, A
AU  - Stevens A
FAU - Wilson, C B
AU  - Wilson CB
FAU - Bassetti, M
AU  - Bassetti M
FAU - Aderem, A
AU  - Aderem A
LA  - eng
SI  - GENBANK/AF185284
SI  - GENBANK/AF185285
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9010-72-4 (Zymosan)
SB  - IM
CIN - Nature. 1999 Oct 21;401(6755):755-6. PMID: 10548095
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Differentiation/metabolism
MH  - CHO Cells
MH  - Cell Line
MH  - Cricetinae
MH  - *Drosophila Proteins
MH  - Macrophages/*metabolism
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Molecular Sequence Data
MH  - Myeloid Differentiation Factor 88
MH  - Phagocytosis
MH  - Phagosomes/*metabolism
MH  - Point Mutation
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - *Receptors, Immunologic
MH  - Recombinant Proteins/genetics/metabolism
MH  - Salmonella/metabolism
MH  - Signal Transduction
MH  - Staphylococcus aureus/metabolism
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptors
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Yeasts/metabolism
MH  - Zymosan/metabolism
EDAT- 1999/11/05 08:00
MHDA- 2001/03/23 10:01
CRDT- 1999/11/05 08:00
PHST- 1999/11/05 08:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/11/05 08:00 [entrez]
AID - 10.1038/44605 [doi]
PST - ppublish
SO  - Nature. 1999 Oct 21;401(6755):811-5. doi: 10.1038/44605.