The body's immune system may be the keeper of a healthy gut microbiota, report University of Chicago scientists on April 21 in the journal Immunity. They found that a single binding protein on white blood cells could affect whether or not mice produced a balanced gut microbiota. Without the protein, harmful bacteria were more easily able to cause infection. Why this happens is unclear, but it may be that the immune system has a way to sense the presence of invading intestinal bacteria.
"Our study reveals how our body's immune system shapes the gut microbiota to naturally limit infections," says senior author Yang-Xin Fu, a professor in the University of Chicago Department of Pathology. "Given the rapid rise of harmful bacteria that are resistant to antibiotics, it is paramount that scientists find methods of limiting harmful bacterial infections without the use of antibiotics. For future patients who are infected with harmful bacteria, it might be beneficial to promote the development of good gut microbiota to indirectly kill harmful bacteria, instead of using antibiotics."
Fu and his collaborators found that intestinal immune cells--called type 3 innate lymphoid cells (ILC3s)--are less able to respond to harmful bacterial infections when they lack a protein called Id2. ILC3s that lacked Id2 were unable to produce a molecule called IL-22 that subsequently stimulates other intestinal cells to produce antimicrobial peptides (AMPs), which help protect the body against pathogenic infections. Notably, normal bacteria seem to be more resistant to AMPs.
When the team transferred microbiota from a mouse with such dysfunctional ILC3s into a completely germ-free mouse, the recipient animal was highly susceptible to infections when later exposed to harmful bacteria. Germ-free mice that received microbiota from animals with functional ILC3s could fight off the bacteria.
How immune cells distinguish between beneficial and harmful bacteria to maintain a healthy microbiota is unknown, although pathogens might produce some molecules that immune cells can sense. After invasion, it has been observed that ILC3s produce higher levels of antimicrobial peptides.
Fu notes that the human body and its microbiota have evolved to live in harmony over millions of years. "This mutually beneficial relationship provides us with the ability to properly receive all of the nutrients from our food, and as shown with this study, the ability to limit harmful bacterial infections," he says.
The work was supported by the National Institutes of Health.
Immunity, Guo et al.: "Innate Lymphoid Cells Control Early Colonization Resistance against Intestinal Pathogens through ID2-Dependent Regulation of the Microbiota" http://dx.
Immunity, published by Cell Press, is a monthly journal that reports the most important advances in immunology research. Topics include: immune cell development and senescence, signal transduction, gene regulation, innate and adaptive immunity, autoimmunity, infectious disease, allergy and asthma, transplantation, and tumor immunology. For more information, please visit http://www.