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Discovery of New Form of Cell Death Offers Clues to Controlling Bacterial Colonization in the Gut

October 2, 2018

PHILADELPHIA (October 2, 2018) — Observing how cells of the intestinal epithelium respond to Salmonella, scientists at Fox Chase Cancer Center have found a novel mechanism of cell death that shows a way to control the spread of bacteria. Siddharth Balachandran, PhD, co-leader of the Blood Cell Development and Function program at Fox Chase, led the research, which appears in The Journal of Immunology.

It is known that Salmonella first infects the lining of the large and small intestine when it is ingested. Balachandran observed that infected cells are rapidly eliminated by a secreted host protein, the cytokine gamma interferon. Exposure of infected, but not uninfected, cells to gamma interferon triggers a novel form of cell death that has not been previously identified.

“This anti-bacterial defense strategy eradicates the infected cell before it can become a factory for Salmonella replication. This helps control bacterial spread to other sites in the body and limits the impact of the disease,” Balachandran said.

This work was done in collaboration with Sergei Grivennikov, PhD, an assistant professor at Fox Chase who studies how immune and inflammatory pathways promote tumor growth and progression.

Salmonella is a leading cause of food- and water-borne illness, affecting as many as 90 million people every year worldwide.

Balachandran is a consultant for Ascend Biopharmaceuticals. The other authors have no financial conflicts of interest. This work was supported by National Institutes of Health Grant R00 DK088589, American Cancer Society Grant 15-175-22, and a Pew Scholar in Biomedical Sciences award to Grivennikov, as well as NIH Grants CA168621, CA190542, and AI113469 to Dr. Balachandran. Additional funds were provided by NIH Cancer Center Support Grant P30CA006927.

       

The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.
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