Immune Tolerance and Pathobionts: Good Guys/Bad Guys

Did you ever wonder how our bodies are able to differentiate between our commensal bacteria and pathogenic ones?  Many times in this blog, I’ve written about this “immune tolerance.”   Researchers at NYU are trying to figure this out and are partly there.[i]

Of course, what makes this even more complicated is that some bacteria are beneficial sometimes, pathogenic at others.  (You can read about a prime example in my post on Helicobacter pylori back in July.)  Scientists have given these types of bacteria a name:  pathobionts.

Using mice and a type of Helicobacter bacteria (H.hepaticus – which is not known to be beneficial at this time, but can be dangerous at others), these researchers tried to clarify, “…the mechanisms that help the body manage the risk of keeping potentially dangerous, but often useful, bacteria around.”[ii]

The found that two types of T cells control the immune response to microbes.  The bacteria produce a yet-unknown molecule (or molecules) which signal the immune system to produce a kind of T cell (T helper 17 (Th17)), that, in turn, triggers an inflammatory response to a pathogenic strain.  Mammals’ immune systems have evolved in such a way that each group of Th17 cells specific to a pathobiont bacteria is “…paired with a second set of T regulatory cells that shuts down those Th17 cells, creating tolerance to the bacterial strain at hand.”

Of course then, defects  in (or lack of) these T reg cells can lead to loss of immune tolerance and an abnormal inflammatory response to various bacteria, such as is seen in inflammatory bowel diseases.  In fact, these NYU researchers will be giving mice gut bacteria from humans with IBD to try to identify the pathobiont species causing the disease.  “”The current work suggests that pathobiont-driven IBD may be dependent on T cells that have escaped the normal tolerance system, attacking bacterial species that do not normally cause inflammation…If confirmed, future treatments may consist of groups of bacterial species or key pieces of them, chosen because they can turn on sets of Tregs to quiet overall gut inflammation.'”

You also have to wonder what role other inhabitants of the biome play in all this.  Helminths, for example, are probably the most potent stimulators of T reg cell production.  And we know too that different protozoa are also pathobionts – is the mechanism the same?  (Read my post on this from last week.)  Is the depletion of the entire eukaryome (all living species that are not bacteria) a key part of this picture?

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[i]Xu, M, et. al. c-Maf-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont, Nature (2018).

[ii] https://medicalxpress.com/news/2018-02-body-potentially-bacteria-disease.html