Toll-Like Receptors Responding to Lipopolysaccharide (LPS)
from the Gram-Negative Cell Wall
and Signaling the Synthesis
Inflammatory Cytokines.

Content on this page requires a newer version of Adobe Flash Player.

Get Adobe Flash player

1) Gram-negative bacteria release lipopolysaccharide (LPS; endotoxin) from the outer membrane of their cell wall.
2) The LPS binds to a pair of TLR-4s on defense cells such as macrophages and dendritic cells. LPS also binds to LPS-binding protein in the plasma and tissue fluid. The LPS-binding protein promotes the binding of LPS to the CD14 receptors. At that point the LPS-binding protein comes off and the LPS-CD14 bind to TLR-4.
3) The binding of LPS to TLR-4 enables regulatory molecules within the cell - Mal, MyD88, Tram, and Trif - to trigger reactions that activate a master regulator of inflammation called NF-kappa B. Activated NF-kappa B enters the cell's nucleus and switches on genes coding for cytokines such as:

a. Interleukin-1 (IL-1) and Tumor necrosis factor-alpha (TNF-alpha): enhance inflammatory responses;
b. Interleukin-8 (IL-8): aids in the ability of white blood cells to leave the blood vessels and enter the tissue; a chemoattractant for phagocytes;
c. Interleukin-6 (IL-6) promotes B-lymphocyte activity; and
d. Interleukin-12 (IL-12): promotes T-lymphocyte activity. (5)

4) Cytokine genes are transcribed into mRNA molecules that goe to the cytoplasm to be translated into inflammatory cytokines that are subsequently secreted from the cell.

Flash animation illustrating Toll-Like Receptors Responding to Lipopolysaccharide (LPS) from the Gram-Negative Cell Wall and Signaling the Synthesis Inflammatory Cytokines.swf by Gary E. Kaiser, Ph.D.
Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://faculty.ccbcmd.edu/~gkaiser/index.html.

Creative Commons License

Last updated: August, 2018
Please send comments and inquiries to Dr. Gary Kaiser