Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2.
Invasive infection with Gram-positive and Gram-negative bacteria often results in septic shock and death. The basis for the earliest steps in innate immune response to Gram-positive bacterial infection is poorly understood. The LPS component of the Gram-negative bacterial cell wall appears to activate cells via CD14 and Toll-like receptor (TLR) 2 and TLR4. We hypothesized that Gram-positive bacteria might also be recognized by TLRs. Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB. CD14 coexpression synergistically enhanced TLR2-mediated activation. To determine which components of Gram-positive cell walls activate Toll proteins, we tested a soluble preparation of peptidoglycan prepared from S. aureus. Soluble peptidoglycan substituted for whole organisms. These data suggest that the similarity of clinical response to invasive infection by Gram-positive and Gram-negative bacteria is due to bacterial recognition via similar TLRs.
Yoshimura
A
A
Maxwell Finland Laboratory for Infectious Diseases, Boston University School of Medicine, Boston Medical Center, MA 02118, USA.
Lien
E
E
Ingalls
R R
RR
Tuomanen
E
E
Dziarski
R
R
Golenbock
D
D
D000818:Animals; D001426:Bacterial Proteins; D016466:CHO Cells; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000276:immunology* / Q000472:pathogenicity; D016908:Gram-Positive Bacterial Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics; D010457:Peptidoglycan / Q000276:immunology / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D013301:Streptolysins / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection / Q000276:immunology
D001426:Bacterial Proteins; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D013301:Streptolysins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C032290:plY protein, Streptococcus pneumoniae