Pneumococcal cell wall activates NF-kappa B in human monocytes: aspects distinct from endotoxin

Area of Science:

• Immunology
• Molecular Biology
• Microbiology

Background:

• Nuclear factor kappa B (NF-kappa B) is a transcription factor central to inflammatory processes and acute phase gene regulation.
• Mice lacking the p50 subunit of NF-kappa B exhibit increased susceptibility to pneumococcal challenge, indicating a role in host defense.
• The specific contribution of pneumococcal components, particularly the cell wall, to NF-kappa B activation requires further elucidation.

Purpose of the Study:

• To investigate the role of NF-kappa B in the host response to pneumococcal cell wall components.
• To identify specific cell types and molecular structures involved in NF-kappa B activation by Streptococcus pneumoniae.

Main Methods:

• Utilized a luciferase reporter assay system to quantify NF-kappa B activation in response to various stimuli.
• Tested NF-kappa B activation in 70Z/3 murine pre-B cells, U937 human monocytes, and THP-1 human monocytes.
• Stimuli included intact pneumococci, pneumococcal cell wall extracts, and lipopolysaccharide (LPS).

Main Results:

• THP-1 human monocytes demonstrated robust NF-kappa B activation by intact pneumococci and cell wall components, unlike 70Z/3 cells and U937 monocytes.
• The response in THP-1 cells was dose- and time-dependent.
• Pneumococcal cell wall activity persisted after modifications to teichoic acid choline or protease treatment, highlighting the glycopeptide backbone's importance.

Conclusions:

• NF-kappa B activation by pneumococci is cell-type specific.
• The glycopeptide backbone of the pneumococcal cell wall appears to be a critical determinant for inducing NF-kappa B-mediated pro-inflammatory responses in certain cells.