October 17, 2017

New Insights on How Pathogens Escape Immune System

A new study at the University of Cologne is trying to decode how the pathogen Salmonella enterica escapes the immune system. And they found a mechanism the bacteria uses.

Salmonella

There were 13,822 reported cases of Salmonella typhimurium in Germany in 2015. In healthy people, most recover without any treatment from antibiotics, but those who are considered “high risk” can suffer serious illness and even death. Those patients include the elderly, the very young, pregnant women, people with chronic illnesses such as diabetes, and those with immune deficiencies.

In those high risk patients, the bacteria cause damage to cells and can get into the bloodstream. If this happens, an infection called “sepsis” occurs, which can be life-threatening.

Salmonella bacteria escape a process called “autophagy,” in which cells clean and degrade pathogens and damaged parts of the cell. The leading author of the study, Dr. Nirmal Robinson, said in a statement, “you can imagine autophagy as the vacuum cleaner of the cell.” This process preserves the function of cellular organelles. As we age, autophagy declines.

The scientists found that two proteins, called Sirtuin 1 and AMPK, which sense changes in metabolism, were reduced upon infection. AMPK detects the loss of energy in the cell, which activates autophagy. Sirtuins also sense metabolism decline. Both are activated when there is an energy demand.

An infection causes an energy loss that enhances autophagy. But after cells were infected with Salmonella bacteria, the proteins required to activate autophagy are degraded in lysosomes in the cells. Robinson said, “the pathogen dismantles the machinery by targeting it for degradation and thereby escaping the immune system.”

The researchers are going to use this information to search for therapeutic applications in the treatment of other diseases like cancer. For instance, cancer cells up regulate autophagy to survive stressful conditions. Scientists hope that they can strengthen or weaken the level of autophagy as it is needed in the treatment of diseases.

Salmonella infections are typically caused by foods such as chicken, eggs, produce, and leafy greens. Salmonella is the leading cause of food poisoning in the United States, sickening a million people every year, and causing 19,000 hospitalizations and 380 deaths.

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