Toll-Like Receptors Responding to GPI-Anchored Proteins
from the Cytoplasmic Membranes of Protozoa
and Signaling the Synthesis
Inflammatory Cytokines.

1) Protozoans release GPI-anchored proteins (GPI = glycosylphosphatidylinositol) from their cytoplasmic membranes.
2) The GPI binds to a TLR-1/TLR-2 pair on defense cells such as macrophages and dendritic cells.
3) The binding of GPI to TLR-1/TLR-2 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.

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