Researchers discover how C. diff red lines immune response

Public release date: 30-Nov-2012 [ | E-mail | Share ]

Contact: Tiffany Trent ttrent@vt.edu 540-231-6822 Virginia Tech

Researchers in the Nutritional Immunology and Molecular Medicine Laboratory at Virginia Bioinformatics Institute have discovered how a common diarrhea-causing bacterium sends the body's natural defenses into overdrive, actually intensifying illness while fighting infection.

The discovery, recently published in PLOS One, may lead to new drug treatments for Clostridium difficile, a common germ in health care-associated infections often referred to as C. diff. It has been linked to the death of 14,000 Americans annually, according to the Centers for Disease Control and Prevention.

Researchers with the Center for Modeling Immunity to Enteric Pathogens at Virginia Tech applied computational and mathematical modeling in combination with RNA-sequencing and mouse studies to understand an important regulatory pathway during Clostridium difficile infection.

"We have found that tissue damage and disease severity in C. difficile infection is associated with a disruption of the peroxisome proliferator-activated receptor gamma (PPAR) pathway," said Josep Bassaganya-Riera, a professor of immunology, director of the Nutritional Immunology and Molecular Medicine Laboratory and the principal investigator with the Center for Modeling Immunity to Enteric Pathogens.

The human intestine must peacefully coexist with trillions of beneficial bacteria while swiftly responding to pathogens such as C. difficile. Sometimes the immune system will go into overdrive when responding to pathogens, causing more damage in an attempt to clear the infection.

Scientists studying mice bowels found the PPARy pathway keeps the immune response in check, allowing the body to heal while the immune cells that fight infection do their work in a controlled manner. When PPARy was absent or inactive, disease was more rampant and colonic lesions from C. difficile were much worse.

In addition, researchers found the protective mechanism can be activated and the severity of the C. difficile infection can be reduced by using an existing diabetes drug. More studies will be needed before the drug can be tested against C. difficile.

"This research demonstrates that the integration of powerful computer simulations of host responses with immunology experimentation not only contributes to a better understanding of the immunoregulatory processes in the gut mucosa during C. difficile infection, but it also advances the discovery of broad-based therapeutic targets in the host for infectious diseases," said Raquel Hontecillas, an assistant professor of immunology at Virginia Tech, co-director of the Nutritional Immunology and Molecular Medicine Laboratory and leader of the immunology component of the Center for Modeling Immunity to Enteric Pathogens.

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Researchers discover how C. diff red lines immune response

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