Autophagy, or Cellular Housecleaning, Controls TB In-Vivo

Built-In Biological Process Can Be Directed To Suppress Disease(s)

13 FEBRUARY 2013, ALBUQUERQUE, NEW MEXICO USA
Summary
Researchers at the University of New Mexico have succeeded in using the body’s own built-in immune system to suppress the worldwide scourge Mycobacterium tuberculosis (TB) and associated inflammation, which also might impact Crohn’s and other inflammatory diseases. By directing the body’s autophagy, or “self-eating,” process in-vivo, researchers have increased control of TB and its associated pathology.

Researchers at the University of New Mexico have succeeded in using the body’s own built-in immune system to suppress the worldwide scourge Mycobacterium tuberculosis (TB) and associated inflammation, which also might impact Crohn’s and other inflammatory diseases.

By directing the body’s autophagy, or “self-eating,” process in-vivo, researchers have increased control of TB and its associated pathology. Autophagy is the vital internal cell-scrubbing process that maintains the intracellular landscape by gathering and disposing of worn-out proteins and invading microorganisms.

UNM Professor and Chair of the Molecular Genetics and Microbiology Department Vojo Deretic, Ph.D., and team, along with a Norwegian team led by Terje Johansen – believe they can direct autophagy in the human body through immunity regulators to prevent excessive inflammation and thus prevent an active TB disease state.

By controlling the bacterial load and suppressing inflammation, autophagy prevents progression to active TB. These findings provide fundamental insight into the immunological function of autophagy and reveal its potential to suppress transmission of tuberculosis, which depends on the development of active disease in infected people.

“Millions of people the world over are infected with tuberculosis, but many don’t have the active disease,” Deretic explains. “By exciting or subduing the autophagy process, we can affect how tissues react to the disease. Inflammation predisposes the cells to active TB. By minimizing inflammation, which directly affects disease pathology, we can keep the disease in a dormant state. Interestingly, active Crohn’s Disease also is directly connected to inflammation, so our ability to control inflammation through autophagy has wide implications, including inflammatory bowel disease, and potentially neurodegenerative diseases like Alzheimer’s disease and dementia with inflammatory components.”

The dual roles of autophagy in controlling the bacterial burden and suppressing the inflammation that leads to active tuberculosis make autophagy an attractive target for development of therapeutics. Currently, Deretic’s team is screening existing FDA-approved anti-inflammatory drugs and candidates to determine new treatments through drug repurposing.

Findings are available in the Proceedings of the National Academy of Sciences, November 13, 2012, under the title, Autophagy Protects against Active Tuberculosis by Suppressing Bacterial Burden and Inflammation. For more information on UNM’s Molecular Genetics and Microbiology Program, visit http://mgm.unm.edu/index.html.

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