Nav: Home

Immunology: Live and let live

March 10, 2017

In order to maintain the microflora in the gut, the immune system must be taught to tolerate foreign bacteria. Ludwig-Maximilians-Universitaet (LMU) in Munich researches have now shown how immune surveillance cells are educated to perform this task.

The fundamental task of the immune system is discrimination -- discrimination between the tissues of its host ('self') and invasive pathogens ('non-self'). In order to turn its destructive powers on the proper targets, it must be capable of distinguishing friend from foe. This poses a particular challenge for the immune cells that are associated with the epithelial lining of the gut. They are exposed to the natural microbiota of the gut, which themselves play an important physiological role. Hence the immune system must in some way be actively prevented from attacking these bacteria although they do not fall into the 'self' category. A German-Italian research collaboration has now uncovered one mechanism that helps to maintain this equilibrium in the gut. The project was led by Professor Thomas Brocker, Director of the Institute for Immunology at LMU, and the researchers report their findings in Nature Communications, an open-access member of the Nature family of science journals.

So-called dendritic cells (DCs) play a key part in maintaining this vital balance. DCs have two quite distinct physiological roles: In cases of infection they are essential for the activation of an immune response, but they are also involved in promoting immunological tolerance, i.e. they are capable of actively suppressing the immune response. In this sense, DCs act both as warriors and as diplomats. In the latter guise they stimulate what are called induced regulatory T-cells (iTregs), which control the development of immunological tolerance and inhibit the activation of the immune system. In order to trigger tolerance vis-à-vis the gut microflora, DCs in the gut epithelium recognize and internalize microbial proteins and migrate to the lymph nodes that are associated with the intestine. On the way, the bacterial proteins are processed into small fragments. These tags are then displayed on the surface of the DCs in association with specific binding proteins that are recognized by regulatory T-cells. This interaction in turn instructs the iTregs to suppress immune responses against the proteins in which these segments occur. "We believe that these iTregs are specific for the proteins produced by natural gut bacteria," says Brocker.

Dendritic cells, in particular those that bear a protein known as CD103+ on their surfaces, migrate to lymph nodes from the gut epithelium, and keep the immune system up to date on the composition of the gut microflora. But the researchers wanted to know how the tolerance edict is 'revoked' in an emergency. They went on to identify a well-known signaling molecule, CD40, as the alarm button. CD40 is a second surface receptor on the DCs. But the interaction of CD40 with its binding partner on so-called effector T-cells turns previously diplomatic DCs into warlike DCs by priming them to trigger rather than inhibit immune responses.

The researchers demonstrated the effects of this transition in an animal model. Mice in which the CD40 signaling relay was permanently activated developed severe colitis, but showed no other symptoms. These dendritic cells can still migrate from the gut epithelium to the lymph nodes. However, once there, they undergo programmed cell death (apoptosis) and therefore cannot alert the regulatory T-cells to ensure the maintenance of immunological tolerance of proteins derived from the gut microflora. As a result, a generalized immune response is activated, and T-lymphocytes migrate to the gut epithelium where they induce inflammation. If these mice are then treated with antibiotics that eliminate the natural microbiota from the intestine, the inflammation subsides and the mice survive. "These findings show that interaction between CD103-positive dendritic cells and regulatory T-cells is essential for the maintenance of the correct immunological equilibrium or homeostasis in the gut," Brocker concludes. He and his colleagues now plan to clarify whether properly programmed regulatory T-cells are in fact specific for members of the gut microbiota, as the present results suggest.

Ludwig-Maximilians-Universität München

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...