Why viruses and bacteria trigger different immune responses

"The core of these findings is that we are revising a central aspect of what we thought we knew about how these proteins worked," says study leader Uwe Vinkemeier. (Credit: James Emery/Flickr)

Scientists have identified a key difference in the way our immune systems respond to viral and bacterial pathogens.

The study, published in the journal Nature Immunology, focused on STAT1, a protein that can bind DNA and hence plays a vital role in regulating genes in the body.

STAT-1 responds to interferon signals. These hormone-like molecules control communication between cells to trigger defensive action by the body’s immune system when pathogens such as bacteria, viruses, or parasites are detected.

The defensive actions are also part of the body’s ability to control the growth of malignant tumors.


Scientists thought that all interferons used single STAT1-containing units rather than STAT1 chains to regulate the activity of genes. However, using mice bred specially to express a mutated form of STAT1—which is limited to forming single STAT1 units—researchers showed that this abolishes the function of some interferons while leaving others largely unaffected.

When the assembly of STAT1 chains was inhibited, type I interferons responsible for protecting against viruses were unaffected, whereas type II interferons, which protect against bacterial infections, no longer functioned effectively.

“The core of these findings is that we are revising a central aspect of what we thought we knew about how these proteins worked,” says study leader Uwe Vinkemeier, a professor in the University of Nottingham’s School of Life Sciences. “The molecular mechanisms underlying type I and type II interferon functioning are actually more distinct than we previously imagined. This in turn offers new options for rational pharmacological intervention.”

For example, type I interferons, involved in the anti-viral response also play a role in stopping cells from growing and replicating—and therefore inhibiting the spread of the virus throughout the body.

These interferons are already in clinical use against hepatitis virus and several cancers and in the treatment of auto-immune diseases like multiple sclerosis.

Type-II interferon, in contrast, has been shown to be detrimental in some of these conditions, namely multiple sclerosis and melanoma.

“In situations like these our finding offers a new target for making current treatments more effective. There is good reason to assume that an inhibitor of STAT1 chain formation could potentially block detrimental type-II interferon responses while keeping type I activities, including anti-viral protection, intact. This would avoid an important shortcoming of current STAT1 inhibitors,” says Vinkemeier.

Researchers from the University of Göttingen Medical Centre and the Max-Planck Institute for Molecular Cell Biology and Genetics in Dresden, the Swiss Tropical and Public Health Institute in Basel, and the University of Vienna in Austria contributed to the research.

Source: University of Nottingham