Scans show immune cells intercepting parasites

December 10, 2008

St. Louis, December 10, 2008 -- Researchers may have identified one of the body's earliest responses to a group of parasites that causes illness in developing nations.

In a paper published online in Public Library of Science Pathogens, scientists report that they tracked immune cells as they patrolled the second-shallowest layer of the skin in an animal model. Injections of a genetically modified form of the parasite Leishmania major caused the immune cells to turn from their patrols and move to intercept the parasites.

The same parasites are now infecting U.S. soldiers on patrol in Iraq and Afghanistan, where sand flies, the insects whose bites spread Leishmania, are endemic. The infections normally do not cause symptoms, but the parasite can reactivate and cause complications during pregnancy or if the immune system weakens, including skin sores, fever, damage to the spleen and liver and anemia.

"This is one of our most detailed looks so far at how a first responder in the immune system scouts out pathogens," says co-author Stephen Beverley, Ph.D., the Marvin A. Brennecke Professor and head of the Department of Molecular Microbiology at Washington University School of Medicine in St. Louis. "Determining how the immune system reacts is critically important for efforts to develop vaccines that protect against these parasites."

According to Beverley, what researchers learn from Leishmania also may have applications for controlling more harmful parasites from the same family of microbes, the trypanosomes. These include Trypanosomiasis, the cause of African sleeping sickness, which disrupts the lymph, circulatory and nervous systems and is fatal if untreated, and Chagas disease, which can damage the heart and the intestine in long-term infections.

The study began with an attempt to better understand the role of a group of immune cells known as dendritic cells in the dermis, the second layer of the skin. Scientists at the University of Pennsylvania created a line of mice genetically modified so their dendritic cells produced a yellow fluorescent protein. They used a technique called two-photon microscopy to track the movements of the cells in living mice and show that the cells were "surprisingly motile around the perimeter, moving about and doing all sorts of patrolling," according to Beverley.

One of Beverley's graduate students, Michael A. Mandell, took a strain of Leishmania genetically modified to produce red fluorescent protein and injected it into the Pennsylvania group's mice. The different colors allowed them to use two-photon microscopy to track both dendritic cells and parasites at the same time, and they found that the dendritic cells rapidly homed in on the injected parasites.

Dendritic cells are antigen-presenting cells, which means they can absorb invaders and then display bits of them on their surface to other immune system cells. This triggers a heightened counterattack against the invaders from a variety of immune cells.

Injections of latex beads did not cause the same response from the dendritic cells.

"The dendritic cells were clearly recognizing something made by the pathogen that was provoking their response, and that's one question we will be looking to answer in follow-up experiments," Beverley says.

Beverley notes that infection with Leishmania and other parasites can cause different diseases in different people, suggesting that genetic differences in parasite and host can alter the immune response. Methods of transmission in the wild are messier than an injection and may also add variety to those responses.

"Many of the insects that pass on these parasites are not elegant eaters--they chew on skin, creating pools of many cell types," he explains. "The big question is: How do all the different immune cell types combine to orchestrate the immune system's response? What we've done is to pull out one leading player from that mix, which is an important first step to understanding the overall response."
-end-
Ng LG, Hsu A, Mandell MA, Roediger B, Hoeller C, Mrass P, Iparraguirre A, Cavanagh LL, Triccas JA, Beverley SM, Scott P, Weninger W. Migratory dermal dendritic cells act as rapid sensors of protozoan parasites. Public Library of Science Pathogens, November 30, 2008.

Funding from the National Institutes of Health, the National Health and Medical Research Council, the New South Wales Life Sciences Award and the Cancer Research Institute supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.