Nav: Home

New insights on how pathogens escape the immune system

March 03, 2017

Our immune system has various ways to deal with threats from the outside like pathogens. One of the defence mechanisms is a process called autophagy. 'You can imagine autophagy as the vacuum cleaner of the cell', says Nirmal Robinson, leading scientist of the study. 'It keeps the cell clean by clearing and degrading pathogens or damaged parts of the cell.' This prevents the toxic accumulation of cellular waste and thus preserves the function of cellular organelles. A decline in autophagy also plays an important role in aging and longevity. If the genes linked to autophagy are deleted in animals like the nematode C. elegans, a decrease in lifespan and early onset of aging can be observed.

For his current research Robinson used the bacterium Salmonella typhimurium. With 13,823 reported cases in Germany in 2015, Salmonella infections belong to the group of common infectious diseases in humans. In healthy patients, symptoms are gone without antibiotic treatment, but in risk groups such as old people or immune-deficient persons, the risk of serious illness remains. This pathogen is known to escape the process of autophagy. The goal of the researchers was to understand how this pathogen identifies these processes and tricks them. They found that two proteins called Sirtuin1 and AMPK, which sense changes in the metabolism, were reduced upon infection. Usually, the loss of energy within the cell is detected by AMPK, and it gets activated resulting in autophagy. Sirtuins are another class of metabolic sensors, and their action is dependent on the metabolite NAD+. Together they help in inducing autophagy when there is an energy demand. During infection, there is an energy loss that would normally enhance autophagy. For Robinson's research, immune cells were infected with the pathogen. As expected, energy levels dropped. One would then expect that AMPK gets activated -- and so it does, but only for a very short time. Although energy levels are low, the activation is not sustained. Further investigations on the process revealed the mechanism. Soon after infection, the proteins required to activate autophagy get degraded in lysosomes (a membranous bag containing degrading enzymes). 'The pathogen dismantles the machinery by targeting it for degradation and thereby escapes the immune system', says Robinson.

Nirmal Robinson hopes to use this improved understanding of the process of autophagy in the search for therapeutic applications. 'We can learn to make use of this pathway.' For example, cancer cells upregulate autophagy to survive stressful conditions and to increase growth. They would like to manipulate the process to strengthen or to weaken the level of autophagy in the way they need it. He compares his research to an everyday situation: 'Pathogens are like burglars. By following a burglar we can also identify where we are weak.' By understanding host-pathogen interaction we can understand more about ourselves and how we are designed to protect ourselves against dangerous threats.
-end-
Original publication:

Ganesan R, Hos NJ, Gutierrez S, Fischer J, Stepek JM, Daglidu E, Robinson N, et al. (2017) Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy. PLoS Pathog 13(2): e1006227. doi:10.1371/journal.ppat.1006227

University of Cologne

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:

How the Immune System Works (The How it Works Series)
by Lauren M. Sompayrac (Author)

The Immune System, 4th Edition
by Peter Parham (Author)

The Immune System Recovery Plan: A Doctor's 4-Step Program to Treat Autoimmune Disease
by Susan Blum (Author), Mark Hyman (Foreword), Michele Bender (Foreword)

Basic Immunology: Functions and Disorders of the Immune System
by Abul K. Abbas MBBS (Author), Andrew H. H. Lichtman MD PhD (Author), Shiv Pillai MBBS PhD (Author)

The Immune System: A Very Short Introduction (Very Short Introductions)
by Paul Klenerman (Author)

Immune System: 101 Natural Ways to Boost your Immune System, Fight Germs, and Live a Healthy Life
by Living in Health (Author)

Boost Your Immune System: Strategies for Strengthening Your Immune System with Foods, Herbs, Stress Management, and More!
by Editors of Publications International Ltd. (Author)

The Immune System Cure: Optimize Your Immune System in 30 Days-The Natural Way!
by Lorna Vanderheaghe (Author)

The Immune System, 3rd Edition
by Peter Parham (Author)

Immune System (Amazing Body Systems)
by Karen Kenney (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Hacking The Law
We have a vision of justice as blind, impartial, and fair — but in reality, the law often fails those who need it most. This hour, TED speakers explore radical ways to change the legal system. Guests include lawyer and social justice advocate Robin Steinberg, animal rights lawyer Steven Wise, political activist Brett Hennig, and lawyer and social entrepreneur Vivek Maru.
Now Playing: Science for the People

#495 Earth Science in Space
Some worlds are made of sand. Some are made of water. Some are even made of salt. In science fiction and fantasy, planet can be made of whatever you want. But what does that mean for how the planets themselves work? When in doubt, throw an asteroid at it. This is a live show recorded at the 2018 Dragon Con in Atlanta Georgia. Featuring Travor Valle, Mika McKinnon, David Moscato, Scott Harris, and moderated by our own Bethany Brookshire. Note: The sound isn't as good as we'd hoped but we love the guests and the conversation and we wanted to...