Protein scouts for dangerous bacteria: How the immune system detects listeria and other bad bacteria

February 23, 2012

Millions of "good" bacteria exist harmoniously on the skin and in the intestines of healthy people. When harmful bacteria attack, the immune system fights back by sending out white blood cells to destroy the disease-causing interlopers. But how do white blood cells know which bacteria are good and which are harmful?

Northwestern University Feinberg School of Medicine researchers studied one type of white blood cell known as a macrophage, which is among the immune system's first to detect and eliminate . The research team, led by Christian Stehlik, John P. Gallagher Research Professor of Rheumatology at Feinberg, discovered that the protein NLRP7 serves as a "scout" in , identifying components in harmful gram-positive bacteria such as and .

The findings will be published in the February 23 issue of the journal Immunity.

"NLRP7 is a novel intracellular pattern recognition receptor that specifically recognizes bacterial cell wall components, known as lipopeptides, in harmful bacteria," says Stehlik, who worked closely with collaborators Andrea Dorfleutner, research assistant professor of medicine at Feinberg, and Yon Rojanasakul, Robert C. Byrd Distinguished Professor and Benedum Distinguished Professor at West Virgina University. "We show that activation of NLRP7 is necessary for eradicating bacterial infections through the formation of protein complexes called inflammasomes, which enable the production of defense factors in ."

Identifying the molecule was complicated, says Sonal Khare, postdoctoral fellow at Feinberg and first author on the research paper, because the family of proteins within macrophages is quite large. "There were 22 likely candidates. To determine which one of these proteins is able to recognize bacteria in macrophages, we had to remove each one of them," she says. Through process of elimination, the team identified NLRP7 as the required protein.

Stehlik says the finding is significant because it contributes to a better understanding of how bacteria such as Listeria and Staphylococcus are recognized by the immune system. Listeria is found in uncooked meats, vegetables, and fruits such as cantaloupes. In 2011, listeria was the cause of the deadliest food contamination outbreak in the U.S. in more than a decade. S. aureus infections are most commonly contracted in hospitals, and 500,000 patients acquire Staphylococcus infections annually in the U.S. Methicillin-resistant S. aureus, or MRSA, strains are highly resistant to commonly-used antibiotics.

Understanding how the immune system recognizes these deadly intruders could one day lead to novel treatment strategies to combat these infections.

"The next phase of research related to NLRP7 and inflammasomes is progressing," says Stehlik. "We are continuing the research to explore mechanisms behind how this NLRP7 inflammasome is formed. We want to know whether we can manipulate this process to make the response stronger. We also will be exploring the use of mouse models in this pathway to study this response in vivo."

Explore further: Trudeau Institute reports new approach to treating Listeria infections

More information: The article, "An NLRP7-Containing Inflammasome Mediates Recognition of Microbial Lipopeptides in Human Macrophages" will be available for download on the journal Immunity's web site.

Related Stories

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 ...

Innate immune system proteins attack bacteria by triggering bacterial suicide mechanisms

May 23, 2011
A group of proteins that act as the body's built-in line of defense against invading bacteria use a molecular trick to induce bacteria to destroy themselves, researchers at the Indiana University School of Medicine have determined. ...

Recommended for you

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Co-infection with two common gut pathogens worsens malnutrition in mice

July 27, 2017
Two gut pathogens commonly found in malnourished children combine to worsen malnutrition and impair growth in laboratory mice, according to new research published in PLOS Pathogens.

Study sheds light on how body may detect early signs of cancer

July 26, 2017
Fresh insights into how cells detect damage to their DNA - a hallmark of cancer - could help explain how the body keeps disease in check.

How genetically engineered viruses develop into effective vaccines

July 26, 2017
Lentiviral vectors are virus particles that can be used as a vaccine to stimulate the immune system to fight against specific pathogens. The vectors are derived from HIV, rendered non-pathogenic, and then engineered to carry ...

Accounting for human immune diversity increases clinical relevance of fundamental immunological research

July 26, 2017
Mouse models have advanced our understanding of immune function and disease in many ways but they have failed to account for the natural diversity in human immune responses. As a result, insights gained in the lab may be ...

Does your child really have a food allergy?

July 24, 2017
(HealthDay)—Many people misunderstand what food allergies are, and even doctors can be confused about how to best diagnose them, suggests a new report from the American Academy of Pediatrics.


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.