Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel communication between intestinal microbes and developing immune cells in the thymus

24.01.2020

Regulation of thymic immune development by intestinal microbes in early life

Newborns face unique immunological challenges immediately after birth. As they depart a relatively sterile fetal environment, they are abruptly exposed to a multitude of foreign antigens, the major burden of which is in the form of the microbiota newly colonizing the gastrointestinal tract.


Complex interplay between intestinal microbes, host TLR2, pDCs and developing cells in the thymus

Credit: Nitya Jain, PhD

These rapidly multiplying foreign invaders represent, by far, the biggest threat to the neonatal immune system, which has to recognize and classify these organisms as benign, commensal or pathogenic.

Research shows that effective "crosstalk" or communication between early microbes and mucosal immune cells is essential to the formation of healthy microbial communities and promotion of a well-functioning immune system.

The cells of the immune system that participate in mucosal immunity develop in an organ called the thymus located under the breastbone above the heart. Until now, it has been unclear if intestinal microbes influence the development of these cells in the thymus in early life.

Researchers at the Mucosal and Immunology Biology Research Center (MIBRC) at Massachusetts General Hospital now report that gut microbes regulate the development of specialized immune cells in the thymus that play a critical role in mucosal tolerance.

The findings of their extensive research were published in Proceedings of the National Academy of Science, USA this week. Nitya Jain, PhD, and colleagues focused their studies on a subset of immune cells that express the transcription factor PLZF. These cells, collectively called innate and innate-like lymphocytes, typically function at the gut mucosal barrier interface and provide immune protection at mucosal sites.

To study the development of these immune cells in the context of gut microbes, researchers monocolonized germ-free mice with a model human commensal, Bacteroides fragilis, and demonstrated that this single species of bacteria could restore the development of PLZF+ innate and innate-like lymphocytes in the thymus of infant mice.

In further proof-of-concept studies, they showed that a mutant B. fragilis lacking expression of Polysaccharide A (PSA) was unable to do the same, suggesting that specific microbial antigens could regulate this early life developmental process.

A similar deficit in these cells was observed in mutant mice that lacked the expression of Toll like receptor 2, a receptor that recognizes bacteria and bacterial components, including B. fragilis PSA, to initiate host protective immune responses.

To understand how this microbial message was delivered to developing thymic cells, Jain's group used a novel mouse model to track the migration of cells from the colon to the thymus. The photo-conversion strategy, developed with the help of MGH's Guillermo "Gary" Tearney's group at the Wellman Center for Photomedicine, was highlighted in the Journal of Visualized Experiments in 2018.

Researchers showed that a class of antigen-presenting cells called plasmacytoid dendritic cells (pDCs) are imprinted by intestinal microbes and migrate from the gut to the thymus in early life to regulate the development of thymic lymphocytes.

For the first time, Jain's group has revealed "a novel communication between intestinal microbes and developing cells in the thymus," says Jain. "It shapes the immune 'repertoire' in early life and affects how the host will respond to disease throughout the lifespan."

The unbalanced development of an infant's gut microbiome is thought to play a role in disease development later in life. Disturbing the microbiota in infancy by antibiotics or diet, for example, has been linked to increased risk of allergies, asthma and autoimmune disorders including celiac disease and Inflammatory Bowel Disease (IBD).

Jain's group demonstrates one mechanistic basis for this observation. They show that thymic PLZF+ cells did not develop efficiently in mice treated with broad-spectrum antibiotics in early life, but mice treated in later life were spared.

Jain says there "appeared to be an early-life time window when developing immune cells in the thymus were particularly susceptible to microbial influence." Additionally, the study shows that microbe-induced altered development of thymic innate and innate-like cells in early life persists into adulthood and leads to increased susceptibility to experimental colitis.

Importantly, disease severity could be moderated by the transfer of PLZF+ cells from mice that developed with normal microbiota in early life, says Jain. She adds, "This has significant implications for the design of strategies to treat autoimmune disorders such as IBD. Our studies point to a previously unexplored pathway that may be developed as an adoptive cell therapy for patients."

MIBRC Director Alessio Fasano, MD notes that growing evidence shows that early development of a healthy immune state requires an ideal symbiotic relationship between developing infants and their community of microorganisms. "How we 'choose' our ideal microbiome to teach our immune system to defend us rather than harm us is still a big question mark. Nitya and her group--for the first time--have shed light on the very early mechanisms that are in charge of establishing a healthy relationship between the human host and the microbiome," says Fasano.

###

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $1 billion and comprises more than 8,500 researchers working across more than 30 institutes, centers and departments. In August 2019 the MGH was once again named #2 in the nation by U.S. News & World Report in its list of "America's Best Hospitals."

Susie Flaherty | EurekAlert!
Further information:
http://dx.doi.org/10.1073/pnas.1915047117

More articles from Health and Medicine:

nachricht Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

nachricht Ultra-thin fibres designed to protect nerves after brain surgery
27.05.2020 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

New 5G switch provides 50 times more energy efficiency than currently exists

27.05.2020 | Information Technology

Return of the Blob: Surprise link found to edge turbulence in fusion plasma

27.05.2020 | Physics and Astronomy

Upwards with the “bubble shuttle”: How sea floor microbes get involved with methane reduction in the water column

27.05.2020 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>