Friday, May 02, 2008

Avian flu

Avian flu doesn't seem to be in the news so much these days, even though it continues to cause a steady stream of new human infections and often fatalities. The most heavily affected country continues to be Indonesia, but other countries that have this year reported avian flu in many domestic birds, and sometimes resulting human deaths, include Egypt, Turkey, India, Pakistan, Bangladesh, Vietnam, China, and South Korea.

An encouraging recent development is that the mechanism responsible for the serious havoc that H5N1 causes in a person's lungs is becoming better understood. It turns out to involve a signaling cascade initiated by toll-like receptor 4 (TLR-4) on the surface of macrophages in the lungs.

Macrophages are leukocytes (white blood cells) that play a role in both innate and acquired immunity. Among other things, under certain circumstances, they can cause prolific production of inflammation-causing cytokines, such as interleukin-1. When produced excessively cytokines trigger "cytokine storms" (see here), which seem to be the major harmful effect of H5N1 infection. Recently reported research gives more detail:

A single pathway for lung damage
TLR-4 is an important receptor in innate immunity, which signals activation via two pathways, TRIF and MyD88. The researchers found that lung injury was mediated exclusively through the TRIF pathway and not via MyD88. Also, the trigger for TLR-4 turned out to be the oxidation of the animals' own lung surfactant, made up of phospholipids. The oxidized phospholipids activates TLR-4, resulting in the cytokine storm that causes much of the lung damage. In order to see whether their results held true outside of the mouse-ICU, researchers tested human and simian lung samples infected with SARS, H5N1, anthrax and monkey pox and found the oxidized phospholipids in each case.

One of the interesting end results of the TRIF pathway is the activation of the NF-κB transcription factor, which in turn upregulates other proteins that stimulate T cell production, inflammation, and other additional immune response.

More: New Strategies Against Bird Flu

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