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Mechanism discovered by which body's cells encourage tuberculosis infection
Date:12/10/2009

ility of blocking or inhibiting molecular mechanisms in the body to prevent or treat infectious diseases as well. "

Earlier studies in the zebrafish by the Ramakrishnan lab demonstrated that TB tubercles were not, as previously thought, the way that the body walls off the bacteria to protect itself. Instead, these nodules (also called granulomas) are hubs for bacteria production and distribution. Uninfected macrophages the body's frontline soldiers that can eat and destroy many bacteria are recruited to the nodules, where they become TB-infected. However, the TB bacteria are able to grow in the macrophages, rather than being killed, likely by dampening the macrophages' defenses.

So by wooing more macrophages into the granuloma, the bacteria can use them to expand further. Some germ-laded macrophages then move to a new location, where they again attract more macrophages. New tubercles form and the scene is repeated.

Ramakrishnan and her research team have identified a molecular mechanism by which the mycobacteria that cause TB induce the body to form these production and distribution nodules. Researchers have long known that TB virulence is associated with a small protein the bacteria secrete, called ESAT-6.

Ramakrishan's group now has found that this secreted bacterial protein induces epithelial cells the cells that make up membranous tissue covers inside the body to produce an enzyme called MMP9. This enzyme has many functions including breaking down gelatin a connective tissue protein -- into its components. In people, the presence of MMP9 is associated with increased susceptibility to infection and worse outcomes. The findings of this new study explain why this might be the case. MMP9 is also implicated in the development of several non-infectious inflammatory conditions, like arthritis, as well as heart disease and cancer.

Epithelial cells were once thought to be bystanders as tuberculosis took hold, accordin
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Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

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