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PMID:11067888

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Citation

Takeuchi, O, Hoshino, K and Akira, S (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J. Immunol. 165:5392-6

Abstract

Toll-like receptor (TLR) family acts as pattern recognition receptors for pathogen-specific molecular patterns. We previously showed that TLR2 recognizes Gram-positive bacterial components whereas TLR4 recognizes LPS, a component of Gram-negative bacteria. MyD88 is shown to be an adaptor molecule essential for TLR family signaling. To investigate the role of TLR family in host defense against Gram-positive bacteria, we infected TLR2- and MyD88-deficient mice with Staphylococcus aureus. Both TLR2- and MyD88-deficient mice were highly susceptible to S. aureus infection, with more enhanced susceptibility in MyD88-deficient mice. Peritoneal macrophages from MyD88-deficient mice did not produce any detectable levels of cytokines in response to S. aureus. In contrast, TLR2-deficient macrophages produced reduced, but significant, levels of the cytokines, and TLR4-deficient macrophages produced the same amounts as wild-type cells, indicating that S. aureus is recognized not only by TLR2, but also by other TLR family members except for TLR4.

Links

PubMed

Keywords

Adaptor Proteins, Signal Transducing; Animals; Antigens, Differentiation/genetics; Antigens, Differentiation/physiology; Down-Regulation/genetics; Down-Regulation/immunology; Drosophila Proteins; Genetic Predisposition to Disease; Hot Temperature; Immunity, Innate/genetics; Interleukin-6/biosynthesis; Macrophages, Peritoneal/immunology; Macrophages, Peritoneal/metabolism; Membrane Glycoproteins/deficiency; Membrane Glycoproteins/genetics; Membrane Glycoproteins/physiology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Myeloid Differentiation Factor 88; Receptors, Cell Surface/deficiency; Receptors, Cell Surface/genetics; Receptors, Cell Surface/physiology; Receptors, Immunologic; Staphylococcal Infections/genetics; Staphylococcal Infections/immunology; Staphylococcal Infections/mortality; Staphylococcus aureus/immunology; Survival Analysis; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors; Tumor Necrosis Factor-alpha/biosynthesis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MYD88

acts_upstream_of_or_within

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2385681

P

  • regulates_o_occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:MYD88

acts_upstream_of_or_within

GO:0032755: positive regulation of interleukin-6 production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2385681

P

  • regulates_o_occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:MYD88

acts_upstream_of_or_within

GO:0050830: defense response to Gram-positive bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2385681

P

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

  • regulates_o_occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032755: positive regulation of interleukin-6 production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

  • regulates_o_occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032755: positive regulation of interleukin-6 production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0044130: negative regulation of growth of symbiont in host

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

regulates_o_occurs_in:(EMAPA:16332)|regulates_o_occurs_in:(EMAPA:17373)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0050830: defense response to Gram-positive bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

Seeded From UniProt

complete


See also

References

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