YOSHIMURA A, LIEN E, INGALLS RR, TUOMANEN E, DZIARSKI R, GOLENBOCK DT; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 775 (abstract no. 1871).

Maxwell Finland Lab. for Infectious Diseases, Boston Univ., Boston, MA

BACKGROUND: Invasive infection with Gram-positive and Gram-negative bacteria often results in septic shock and death. However, in comparison to the current knowledge concerning Gram-negative bacterial pathogenesis, the basis for the earliest steps in innate immune response to Gram-positive bacterial infection is poorly understood. The lipopolysaccharide component of the Gram-negative bacterial cell wall appears to activate immune cells via CD14 and Toll-like receptor (TLR) 2 and TLR4. We hypothesized that Gram-positive bacteria, which do not synthesize lipopolysaccharide, might also be recognized by TLRs.METHOD: Chinese hamster ovary (CHO) fibroblasts, which do not express a functional TLR2 transcript, were transfected with TLR2 or TLR4 (the putative LPS signal transducer). These cells were exposed to heat-killed Staphylococcus aureus or Streptococcus pneumoniae, and were subsequently subjected to the proinflammatory transcription factor NF-k B translocation assay. In order to determine which components of Gram-positive cell walls might activate Toll proteins, we tested a soluble preparation of peptidoglycan prepared from S. aureus.RESULTS: Heterologous expression of human TLR2, but not TLR4 in CHO cells conferred immune responsiveness to S. aureus and S. pneumoniae as evidenced by the inducible translocation of NF-k B. Although TLR2 expression was sufficient to impart the ability to respond to Staphylococci, CD14 co expression synergistically enhanced TLR2-mediated cellular activation. A soluble preparation of peptidoglycan prepared from S. aureus substituted for whole organisms.CONCLUSION: Expression of TLR2 but not TLR4 rendered CHO cells ressponsive to Gram-positive bacterial cell wall components. 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 receptor systems.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Antigens, CD14
• CHO Cells
• Cell Wall
• Cricetinae
• Female
• Gram-Negative Bacteria
• Gram-Positive Bacteria
• Humans
• Lipopolysaccharides
• Membrane Glycoproteins
• Peptidoglycan
• Receptors, Cell Surface
• Signal Transduction
• Toll-Like Receptor 2
• immunology

Other ID:

• GWAIDS0008560

UI: 102246057

From Meeting Abstracts