We know that good, or "friendly," bacteria work with our immune system to help keep us healthy, but the mechanism behind this remains unknown. New research adds a crucial piece to the puzzle by finding a cellular dynamic that may explain the microbiota's key role.
The link between our gut bacteria and immune system is complex and crucial to our health.
Recent studies have started to reveal parts of this link, but a lot remains undiscovered.
As some researchers have put it, "A huge proportion of your immune system is actually in your [gastrointestinal] tract." So, how do bacteria and the immune system interact?
New research now illuminates part of the answer to this question. It reveals that the "friendly" bacteria collaborate with both the cells that line the inside of our intestines and with immune cells to regulate the immune system's response to infection.
Gretchen Diehl — an assistant professor of molecular virology and microbiology at Baylor College of Medicine in Houston, TX — is the corresponding author of the study, the findings of which are published in the journal Immunity.
How does the microbiota fight off infection?
Prof. Diehl and team carried out a series of in vitro and in vivo experiments using the Salmonella typhimurium microbe to study the intestine's immune response.
Prof. Diehl gives some background information for the research, explaining what is already known about how the intestine and the immune system work together to fight off damaging microbes.
"Disease-causing microbes, such as Salmonella, evoke a strong inflammatory immune response that is directed at eliminating the microbe," she says. "But an inflammatory immune response, especially in the intestine, can be damaging to the healthy tissue."
So what happens is that antigen-presenting immune cells "tell" other immune cells, called T cells, to "gear up" and emit an immune response when they are under siege by strange microbial invaders.
However, antigen-presenting cells also have another role: they tell another type of T cell, known as regulatory T cells, not to have such a strong inflammatory response to things such as the food we ingest. They also tell regulatory T cells to switch off the inflammatory response altogether when necessary.
To switch off, or tone down, this inflammatory response, antigen-presenting cells secrete an anti-inflammatory molecule: the cytokine IL-10.
According to Prof. Diehl, "The result is a balanced response that still can fight off an infection like Salmonella, but that is regulated to prevent damage to the healthy intestinal tissue."
'We wanted to know how the microbiota could induce these kind[s] of responses."
Healthy microbiota drives balanced response
The researchers found that the friendly bacteria interact with both the epithelial cells that line the inside of our gut and with our immune cells to find the right "dosage" of the immune response.
"We found that when we gave the laboratory animals antibiotics, the antigen-presenting cells did not make IL-10."
"When we put back bacteria in the animals' guts, only bacteria that could attach to the intestinal epithelium triggered IL-10 production by antigen-presenting cells and reduced the inflammatory response," Prof. Diehl explains.
"It's somewhat counterintuitive because microbes that can attach to the intestinal epithelium are thought of as pathogens that can potentially cause disease."
"But, in this case we found that the attachment of bacteria to the epithelium was not causing disease; on the contrary, it was necessary to promote a balanced regulation of the T cell responses and helped protect the gut," she says.
Prof. Diehl and team acknowledge that their findings are only one piece of the puzzle, and that many more mechanisms by which gut bacteria keep us healthy have yet to be revealed.
"A take-home message for us is that a healthy microbiota is necessary to allow for a balanced response to not only protect us from infection, but also to limit potential tissue damage as the immune system attempts to eliminate pathogens."
Prof. Gretchen Diehl