Our body’s relationship with bacteria is complex. While infectious bacteria can cause disease, our gut also teams up with “good” bacteria that contribute to nutrition and help us stay healthy. But even the “good” ones can have bad effects if these bacteria end up in tissues and organs where they are not supposed to be.
Now, research published in Nature reveals insight into how the body maintains this balance. Investigations in mice show that the beginning of life is a critical time when the immune system learns to recognize gut bacteria and sets up surveillance to keep them under control. Flaws in these mechanisms could help explain why the immune system sometimes attacks good bacteria in the wrong place, causing the chronic inflammation responsible for inflammatory bowel disease, the study authors say.
“From the moment we are born, our immune system is set up so that we can learn as much as possible to distinguish the good from the bad,” says Matthew Bettini, Ph.D., associate professor of pathology at U of U Health and coauthor with Sloan Kettering Institute immunologist Gretchen Diehl, Ph.D. “Our studies clearly show that there is a window in which the gut microbiota has access to the immune education process. This opens up possibilities for conception. therapies that can influence the trajectory of the immune system at this early stage. “
Definition of limits
By seeking to understand how the body maintains a healthy relationship with bacteria, Bettini, Diehl and their colleagues discovered how the resident gut microbiota shapes the developing immune system. They found that specialized immune cells capture pieces of bacteria and transport them long distances from the intestine to the thymus. Located in the chest, above the heart, the thymus is a gland responsible for “educating” immune T cells. Delivery of the cargo prompts the thymus to produce T cells targeted to the microbiota. Then the T cells leave the thymus to monitor the lymph nodes, intestine, and other sites to keep bacteria under control.
Scientists identified these steps by inoculating the intestines of mice with a certain type of bacteria. In response, the thymus gland produced T cells that specifically recognized these bacteria. However, the scientist did not know how this had happened.
The discovery of the DNA of bacteria present in the thymus and lymph nodes was the first clue that the microbiota had migrated to these sites. To trace their journey, the researchers used specially designed mice whose cells fluoresced red after being exposed to a laser. Within two days of photoactivation, the red cells in the intestine eventually made their way to the thymus, lymph nodes, and spleen.
These processes were robust during the first weeks of life, but declined dramatically by the time the mice reached adulthood.
“Our study challenges previous assumptions that potential pathogens have no influence on immune cells that develop in the thymus,” says Bettini. “Instead, we see that there is a window of opportunity for the thymus to learn from these bacteria. Even though these events that shape the T cells present occur early in life, they may have a greater impact. important later in life. “
This notion was made evident by the discovery that T cells programmed to target beneficial bacteria could act as a defense against closely related “bad” bacteria. Mice populated by E. Coli at a young age were more than six times more likely to survive a lethal dose of Salmonella later in life. The results suggest that boosting immunity to the microbiota also boosts protection against harmful bacteria the body has yet to encounter.
Immersing yourself in these early communications between the body and the microbiota demonstrates how important it is to prime the immune system early on, says Bettini. “This early education of immune T cells is absolutely necessary to rapidly develop a large repertoire of cells to protect us.”
“We believe our findings can be extended to areas of research where certain bacteria have been shown to be either protective or pathogenic for other conditions, such as type 1 and type 2 diabetes,” says Bettini. “Now we wonder if this window of bacterial exposure and T cell development will also be important in triggering these diseases?”
In addition to the U of U Health and the Sloan Kettering Institute, the study co-authors were affiliated with Baylor College of Medicine and the Washington University School of Medicine.
The research published under the title “Thymic development of specific T cells of the intestinal microbiota” in Nature was supported by the National Institutes of Health, the Kleberg Foundation, the Kenneth Rainin Foundation and a Leukemia and Lymphoma Society Scholar Award.