The Immune System’s Mechanisms of Tolerance for Gut Bacteria

Our immune system’s primary function is to identify and eradicate harmful bacteria, detritus, and intruders from the body. How, therefore, does it handle the billions of microbial cells that make our intestines their home? We now know the answer to this question, and the information that scientists uncovered has also altered our understanding of the connections between immunological receptors and a protein called flagellin, which aids bacteria in their motility. Science Immunology has published the results.

Numerous helpful bacteria reside in the human gut microbiome, and humans rely on them for a variety of essential functions. However, there are also harmful bacteria in the stomach. Toll-like receptor 5 is one kind of immunological receptor that may identify these harmful microorganisms (TLR5). Flagellin is a protein present in the bacterial flagellum, which is responsible for the propulsion of bacterial cells. TLR5 binds to flagellin. An inflammatory response is initiated upon TLR5 binding to flagellin.

It’s important to note that not only pathogenic bacteria contain flagellin; many other types of bacteria do as well. Some bacteria have evolved to produce flagellin that does not bind to TLR5, preventing the activation of the immune system in response to the threat. However, many “commensal” or “harmless” bacteria still produce flagellin, and it binds to TLR5. However, the immune system seems to accept these microorganisms in some way.

In this study, the flagellins produced by several bacteria were studied in detail. About half of the 116 flagellin proteins tested were discovered to be unique; these proteins were able to attach to TLR5 like any other, but unexpectedly did not trigger an inflammatory response. These flagellin proteins have been dubbed “silent flagellins” by the study’s authors. This has showed how the immune system tolerates commensal gut bacteria, even when those germs have shared traits with pathogens.

TLR5 binding was previously assumed to be sufficient to activate an inflammatory cascade, but this study disproves that assumption.

Senior study author and head of the Department of Microbiome Science at the Max Planck Institute for Biology Tübingen, Ruth Ley, remarked that the findings showed that bacterial flagellin can interact with TLR5 in at least three distinct ways: bind and induce an immune response; bind and not induce an immune response; and evade by not binding.

Ley elaborated, saying, “It’s astonishing how adjustable the TLR5 receptor’s response is.”

Silent flagellins were revealed to be common among the human gut microorganisms after the researchers analyzed the genomes of a large number of these organisms.

The Max Planck Society, Science Immunology, and other sources