As the world focuses on the Ebola outbreak, a team of Duke researchers are turning their attention to a different infectious disease—the bubonic plague.
The work comes out of the Duke-National University of Singapore Graduate Medical School and investigates the unique pathway taken by the bacteria responsible for the plague. Recently published in the medical journal Immunity, the findings on the mechanism behind the plague may shed light on some infectious diseases’ unconventional methods of attacking the immune system and could potentially yield more effective drug treatments.
“With the current interest in Ebola and the fact that there are no effective anti-virals against it, it’s important to understand more about the immune system and then try to use our immune system to fight against these infections,” said Soman Albraham, senior author of the study and a professor of pathology.
The study details how human immune cells hide bacteria known as Yersinia pestis and transport them to the lymph nodes instead of destroying them—allowing the bacteria to enter the lungs and bloodstream.
“Yersinia is obviously a very virulent pathogen, and we want to know how it’s occurring, basically,” said Ashley St. John, assistant professor in the Emerging Infectious Diseases program at Duke-NUS and lead author of the study. “Usually lymph nodes are not infected by pathogens because they’re supposed to be a fortress of the immune system, but in this case we have a pathogen that’s actually using the lymph nodes to spread.”
In studying the bacteria, St. John and six other researchers hoped to find out exactly what role lymph nodes play in the spread of infection in the body. Lymph nodes, which St. John also calls the command center of the immune system, typically become swollen when targeted by bacterial infection. These swollen lymph nodes are hallmark signs of the plague.
Immune cells usually break down harmful pathogens as one of the body’s main defenses against disease, but in the case of Yersinia, St. John found that the bacteria actually hijack the immune cells and are trafficked to the lymph nodes and circulated through blood, spreading to various parts of the body. Once in the blood, the bacteria can be taken up by a flea and spread to new hosts, St. John said.
“Now that we understand this mechanism of how the bacteria are moving, there could be drugs that can block their spread by affecting the trafficking in the immune cells,” St. John said.
These drug treatments may come from the same drugs that are used to prevent the spread of cancer cells throughout the body, since immune cells carry the bacteria in a similar way, Albraham said.
“[In our study], we used a drug that’s in clinical trials for cancer,” St. John explained. “It blocks the cells from exiting the lymph nodes and prevents them from reaching circulation again.”
Researchers at Duke-NUS believe that focusing on regulating the immune system rather than targeting the pathogens themselves could lead to better treatments and clinical intervention, especially in infectious diseases that might spread by hijacking immune cells in the same pathway that Yersinia does, Abraham noted.
Duke-NUS's program of emerging infectious diseases is one of five signature research programs at the school.
“For me, [Duke-NUS] is important because I study pathogens that don’t evoke conventional immune responses – they use your immune system against you,” said St. John, who completed graduate school at Duke. “It’s interesting to tease apart what’s happening in tropical regions like Southeast Asia where emerging infectious diseases are a really big concern.”
Duke-NUS began in 2005 as a partnership between the Duke School of Medicine and the National University of Singapore.
“It’s a really exciting environment and such a great place,” St. John said. “There’s a lot of movement back and forth between Duke and Duke-NUS. To me, it feels like an extension of the Duke community, even though NUS has many cultural differences and aspects unique to Singapore.”
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