Trudeau Institute reports new approach to treating Listeria infections

October 17, 2011

Research underway at the Trudeau Institute could lead to new treatments for people sickened by Listeria and other sepsis-causing bacteria. Dr. Stephen Smiley's laboratory has published a study in the scientific journal Infection and Immunity that supports a new approach to treating these infections.

Listeria can cause serious illness, especially among the elderly, the very young and those with compromised immune systems. The bacteria can also cause significant complications in pregnant women, including miscarriage.

The is reporting that one miscarriage and 23 deaths can be attributed to a recent outbreak of Listeria infections in the United States caused by tainted cantaloupes; 116 persons from 25 states have been infected with the outbreak-associated strains.

of Listeria usually causes a limited ; however, the bacteria sometimes spread to other parts of the body, resulting in a deadly sepsis. Despite decades of medical research, severe infections caused by Listeria and other bacteria that cause sepsis, like , still threaten .

The Trudeau Institute study demonstrates that mice that have been genetically modified so they cannot produce factor XI (FXI), a specific blood-clotting factor, have an improved capacity to withstand injection with high doses of Listeria. The study also shows that normal mice treated with both an antibody targeting FXI along with antibiotics show improved survival during septic Listeria infection, as compared with mice treated with antibiotics alone.

These findings suggest FXI-targeted therapeutics may be useful for treating severe infections caused by Listeria and other sepsis-causing bacteria.

This recent work builds on a long history of Listeria research at the Trudeau Institute. In the 1960s the Institute's first director, Dr. George B. Mackaness, advanced the use of mouse models to study how cells of the combat Listeria. He discovered that activated play a critical role in killing Listeria. He also discovered that lymphocytes, another type of immune cell, orchestrate this killing response. These seminal observations remain the foundation for modern studies of cell-mediated defense against pathogens.

The Trudeau Institute's second director, Dr. Robert J. North, extended this work by identifying the key subset of anti-Listeria lymphocytes: T cells. Dr. North and his Trudeau colleagues also described crucial roles for NK cells and neutrophils.

Several years ago, Dr. Smiley discovered that blood-clotting proteins also play critical protective roles during immune defense against Listeria. "I was really intrigued by our finding that clotting protects against Listeria because so many other studies had shown that clotting clogs blood vessels and contributes to organ failure and death during septic infections," said Dr. Smiley.

"Our finding suggested that some degree of blood clotting is essential for effective immune defense, but too much is harmful. We set out in search of ways to prevent the bad clotting while maintaining the good."

Specifically, Dr. Smiley's lab looked for clotting factors that appeared to be hyperactive in the septic state.

"The paper we've just published is our first demonstration of this exciting new approach to treating – we found that FXI is overproduced during septic Listeria infections and that therapeutics targeting FXI can reduce septic disease while maintaining immune defense."

Explore further: Researchers announce discovery in fight against sepsis

Related Stories

Researchers announce discovery in fight against sepsis

July 11, 2011

New research from the Trudeau Institute may help to explain why anticoagulant therapies have largely failed to extend the lives of patients with sepsis. The study was led by Deyan Luo, a postdoctoral fellow in Stephen Smiley's ...

Infected cantaloupes have killed 18 in US

October 4, 2011

Eighteen people have died and 100 people have fallen ill since late July in the United States from eating cantaloupes infected with listeria, health authorities said Tuesday.

Recommended for you

Monkeys in Asia harbor virus from humans, other species

November 19, 2015

When it comes to spreading viruses, bats are thought to be among the worst. Now a new study of nearly 900 nonhuman primates in Bangladesh and Cambodia shows that macaques harbor more diverse astroviruses, which can cause ...

One-step test for hepatitis C virus infection developed

November 14, 2015

UC Irvine Health researchers have developed a cost-effective one-step test that screens, detects and confirms hepatitis C virus (HCV) infections. Dr. Ke-Qin Hu, director of hepatology services, will present findings at the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.