Toll-Like Receptors Responding to Fungal Mannans
from the Cell Wall of Yeast
and Signaling the Synthesis
Inflammatory Cytokines.

1) Yeasts release fungal mannans, lipoteichoic acids, glycolipids, and zymosan from their cell wall.
2) The mannans bind to a TLR- 4 receptors on defense cells such as macrophages and dendritic cells.
3) The binding of fungal mannans 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.

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