Nav: Home

How the tuberculosis vaccine may protect against other diseases

December 06, 2016

The tuberculosis vaccine is well known to help protect against other infectious diseases, as well as cancer, but the exact mechanisms have not been clear. A study published December 6 in Cell Reports now shows that the broad-spectrum effects of the Bacillus Calmette-Guerin (BCG) vaccine--the most widely used vaccine in the world--could be mediated by metabolic and epigenetic changes in white blood cells called monocytes through a process called trained immunity. This discovery could pave the way for strategies that combine immunological and metabolic stimulation to boost the effectiveness of vaccines and anti-cancer therapies.

"The implications of these findings are double: On the one hand, we have uncovered new biological interactions that link cellular metabolism with immune responses, and on the other hand, we have opened the door for new therapeutic approaches in which metabolism modulators modulate innate immune responses and can serve as potential novel immunotherapies," says senior study author Mihai Netea of Radboud University Medical Center. "However, what it is important to realize is that this is the beginning of the process to bring this to clinical practice, and more studies are needed for that."

Many epidemiological studies have demonstrated BCG's capacity to protect against infections other than tuberculosis. For example, early administration of the BCG vaccine reduces child mortality, mainly due to a reduction in lower respiratory infections and harmful immune responses triggered by infections. BCG is also used to treat bladder cancer and appears to be beneficial in several other conditions, including asthma and parasitic diseases. However, it has not been clear exactly how BCG exerts its wide-ranging effects.

To address this question, Netea and his team examined BCG-induced metabolic changes in innate immune cells called monocytes. They found that vaccination induced a strong, long-lasting increase in glycolysis and, to a lesser extent, glutamine metabolism in mice and humans. This shift in glucose metabolism toward glycolysis was necessary to trigger trained immunity. This process relies on epigenetic changes, which affect gene activity without altering the DNA sequence, to enhance the ability of innate immune cells to recognize and mount more effective responses against previously encountered pathogens.

Specifically, BCG-induced metabolic changes were required to induce modifications to proteins called histones, which act as scaffolds around which DNA wraps. In the human cohorts, single-nucleotide variations in genes encoding glycolysis enzymes affected the induction of trained immunity in monocytes. Taken together, the results show that cellular metabolism reprogramming is a central process involved in BCG-induced trained immunity.

"These findings change the concept that the innate immune system cannot adapt in the long-term after an infection or vaccination," Netea says. "The whole concept that the function of innate immune cells can change in a stable way, for example, being improved by certain vaccines such as BCG, is a paradigm shift in immunology, as until not too long ago it was assumed that only the adaptive immune system can adapt to previous infections or vaccinations."

Host immune responses are classically divided into innate immune responses, which react rapidly and nonspecifically upon encountering a pathogen, and adaptive immune responses, which are slower to develop but are specific and build up immunological memory, Netea explains. The discovery of trained immunity has challenged the dogma that only adaptive immunity can build immunological memory.

According to Netea, the next step is to conduct a bigger, broader analysis of circulating monocytes in BCG-vaccinated individuals at risk for infections. "In the future, bigger studies should assess inter-individual variation in these responses, in order to be able to identify which factors influence vaccination responses at the level of a person," Netea says. "In the end, a better understanding of BCG-induced trained immunity could lead to the development of strategies that alter cellular metabolism pathways to improve human host defense mechanisms and boost the effectiveness of vaccines and immunotherapy in patients."
-end-
The researchers were supported by the European Research Council; the Netherlands Organization for Scientific Research; the Northern Portugal Regional Operational Programme, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund; and the Fundação para a Ciência e Tecnologia.

Cell Reports, Arts et al.: "Immunometabolic pathways in BCG-induced trained immunity" http://www.cell.com/cell-reports/fulltext/S2211-1247(16)31552-2

Cell Reports (@CellReports), published by Cell Press, is a weekly open-access journal that publishes high-quality papers across the entire life sciences spectrum. The journal features reports, articles, and resources that provide new biological insights, are thought-provoking, and/or are examples of cutting-edge research. Visit: http://www.cell.com/cell-reports. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Tuberculosis Articles:

Old target, new mechanism for overcoming tuberculosis resistance
In strains of tuberculosis that have developed drug resistance mutations, researchers have identified a secondary pathway that can be activated to reinstate drug sensitivity.
Researchers use tiny 3-D spheres to combat tuberculosis
Researchers at the University of Southampton have developed a new 3-D system to study human infection in the laboratory.
How the tuberculosis vaccine may protect against other diseases
The tuberculosis vaccine is well known to help protect against other infectious diseases, as well as cancer, but the exact mechanisms have not been clear.
Tuberculosis bacteria find their ecological niche
An international team of researchers have isolated and analyzed genetically tuberculosis bacteria from several thousand patients from over a hundred countries.
Tuberculosis and HIV co-infection
The HIV virus increases the potency of the tuberculosis bacterium (Mtb) by affecting a central function of the immune system.
Scientists explain why Russian tuberculosis is the most infectious
Scientists conducted a large-scale analysis of the proteins and genomes of mycobacterium tuberculosis strains that are common in Russia and countries of the former Soviet Union and found features that provide a possible explanation for their epidemiological success.
Tuberculosis elimination at stake
New data released by the European Centre for Disease Prevention and Control and WHO/Europe show that an estimated 340,000 Europeans developed tuberculosis in 2014, corresponding to a rate of 37 cases per 100,000 population.
Curcumin may help overcome drug-resistant tuberculosis
New research indicates that curcumin -- a substance in turmeric that is best known as one of the main components of curry powder -- may help fight drug-resistant tuberculosis.
Stopping tuberculosis requires new strategy
Unless there is a major shift in the way the world fights tuberculosis -- from a reliance on biomedical solutions to an approach that combines biomedical interventions with social actions -- the epidemic and drug resistance will worsen, say researchers at Harvard T.H.
Tulane researchers working on new tuberculosis vaccine
Researchers at the Tulane National Primate Research Center are leading efforts to find a new vaccine for tuberculosis, one of the world's deadliest diseases.

Related Tuberculosis 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

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...