Tuberculosis survives by using host system against itself, study finds

December 5, 2018 by Jessica Sieff, University of Notre Dame
Jeff Schorey talks with an undergraduate researcher. Credit: Matt Cashore/University of Notre Dame

In a new study published in the Journal of Experimental Medicine, scientists at the University of Notre Dame have discovered that the pathogen Mycobacterium tuberculosis (MTB) releases RNA into infected cells. This RNA stimulates the production of a compound known as interferon beta that appears to support the growth of the pathogen.

As part of the study the researchers found that mice lacking a key protein required for responding to foreign RNA and therefore required for interferon beta production were better able to control the MTB infection. The discovery was a surprise to the researchers, as interferon beta is essential to controlling several .

"The results suggest that our immune response to mycobacterial RNA is beneficial for the pathogen and bad for the host. It's the total opposite of viral infections," said Jeff Schorey, George B. Craig Jr. Professor in the Department of Biological Sciences at Notre Dame and co-author of the study. "This study gives us a better understanding of how the mycobacteria causes disease and what makes it the most successful pathogen in human history."

MTB infections cause a battle between the immune response and the ability of the bacteria to circumvent that response—who wins the battle determines the body's ability to control the . Schorey and Yong Cheng, a research assistant professor at Notre Dame, set out to determine how mycobacteria RNA could be affecting the host response. What they found was that by releasing RNA, the bacteria set off a chain reaction inside the macrophage, a cell type of the immune system—resulting in a mechanism that benefits the survival of MTB through the production of interferon beta.

While researchers have long known that bacteria produce proteins and other compounds to modulate an , such a role for mycobacterial nucleic acids has only recently been defined. In viral infections, as opposed to bacterial infections, the virus releases its nucleic acids as it needs the machinery of the host cell to help make viral proteins and replicate its genome. In contrast, bacteria already have the machinery for these processes in place, suggesting the release of RNA into the host cell is intentional. The authors found that the MTB use its secretion system known as SecA2 to mediate RNA release from the mycobacteria.

"Bacteria have everything they need to make their proteins, so the fact that they were releasing nucleic acids was a surprise," Schorey said. "These bugs are using this RNA-sensing pathway, which has evolved to promote antiviral activity—so in other words, the bacteria are manipulating our own immune system against us."

MTB is the No. 1 cause of death by an infectious organism, and kills up to 1.8 million people each year. The World Health Organization estimates 200,000 of those deaths are children. Health officials lack an effective vaccine against pulmonary tuberculosis, and antibiotics used to treat the disease must be taken for six to nine months—a daunting regimen that challenges patient compliance. The disease is prevalent in parts of the world where health care systems lack infrastructure and funding.

Despite those challenges, Schorey, an affiliated faculty member at Notre Dame's Eck Institute for Global Health, said the study's results show potential for the development of immunotherapies to selectively stimulate protective immune responses as a treatment option for MTB and other bacterial infectious diseases. 

Explore further: Tuberculosis—the disease of antiquity

Related Stories

Tuberculosis—the disease of antiquity

March 27, 2017
In the time it takes to read this article, half a dozen people will have died from tuberculosis (TB).

Newfound mechanism may yield ways to counter mistaken immune attack on body

November 27, 2018
A newfound genetic regulatory mechanism may shape the immune system's ability to fight viral infections, and play a key role in autoimmune diseases that occur when immune cells attack bodily tissues.

'Double agent' in the immune system may make us vulnerable to bacterial infections

October 4, 2018
Scientists at Scripps Research have discovered the role of an immune system double agent. This molecule, called USP18, can help curtail immune responses, but it can also open the door to bacterial infections, such as harmful ...

Immune receptor provides protective immunity against Group A Streptococcus

October 31, 2018
Group A Streptococcus (GAS), sometimes known as "flesh-eating bacteria," causes invasive infections that result in high mortality. GAS is susceptible to many antibiotics, but continues to cause devastating infections. Many ...

Scientists discover new way that HIV evades the immune system

April 17, 2018
Scientists have just discovered a new mechanism by which HIV evades the immune system, and which shows precisely how the virus avoids elimination. The new research shows that HIV targets and disables a pathway involving a ...

Recommended for you

HIV vaccine protects non-human primates from infection

December 14, 2018
For more than 20 years, scientists at Scripps Research have chipped away at the challenges of designing an HIV vaccine. Now new research, published in Immunity, shows that their experimental vaccine strategy works in non-human ...

RNA processing and antiviral immunity

December 14, 2018
The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

The 'greying' of T cells: Scientists pinpoint metabolic pathway behind age-related immunity loss

December 13, 2018
The elderly suffer more serious complications from infections and benefit less from vaccination than the general population. Scientists have long known that a weakened immune system is to blame but the exact mechanisms behind ...

Scientists create most accurate tool yet developed to predict asthma in young children

December 13, 2018
Scientists at Cincinnati Children's Hospital Medical Center have created and tested a decision tool that appears to be the most accurate, non-invasive method yet developed to predict asthma in young children.

New genetic study could lead to better treatment of severe asthma

December 12, 2018
The largest-ever genetic study of people with moderate-to-severe asthma has revealed new insights into the underlying causes of the disease which could help improve its diagnosis and treatment.

Researchers discover unique immune cell likely drives chronic inflammation

December 11, 2018
For the first time, researchers have identified that an immune cell subset called gamma delta T cells that may be causing and/or perpetuating the systemic inflammation found in normal aging in the general geriatric population ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.