Microbial Good Versus Evil…How Do Our Immune Systems Know?

Like me, many of you may have regularly pondered the question, “How does the human body know which bacteria are good and which are pathogenic?”  🙂  Until today, I had never read anything explaining the mechanism.

Researchers at Caltech are trying to come up with the answer.[i]  To start figuring it out, they used the bacteria  Bacteriodes fragilis, which is abundant in the large intestines of many mammals including humans, and is known to protect mice from inflammatory and neurological disorders, including IBD and multiple sclerosis.  Apparently, there are multiple strains of the bacteria, but healthy people only host one of these.

So, what it is that allows these beneficial bacteria to colonize us long-term and to not be killed off by our immune system like pathogenic ones?

First, the researchers established that the organism clumps together deep within the mucus lining of the gut.  They theorize that such a “…spatial niche is necessary for a single species to settle in and establish a stable foothold.”  They then determined what it is about the organism that permitted this ability to establish such a niche.  Like many pathogenic bacteria, this bacterium is encased in a thick capsule made of carbohydrates.  Bacteria that do not have such a capsule though cannot establish themselves in the mucosal lining.

Here’s where it gets really interesting – and really mysterious.  Our immune systems do recognize the B. fragilis and form antibodies to it.  These antibodies (IgA, the main immune antibody of the gut), which in the case of pathogens mark the invader so it is rapidly destroyed by immune cells, bind to the B.fragilis and help it stick to the epithelial cells in the mucus lining!  That is just amazing.

Says one of the researchers, “It is surprising to find that an immune response actually helps beneficial bacteria to thrive, which in turn helps the host thrive….The study of immunology has mainly been in the context of pathogenic bacteria. But there are trillions of bacteria in the gut, and most of the time none of them are making you sick. Our study shows that there is active immune recognition of these bacteria, but it helps rather than hinders them. This suggests that the immune system is more than just a defense system and antibodies are more than just weapons.”[ii]

Right now, they have absolutely no idea how this works – why it is that these antibodies switch function when confronted with a commensal organism.  That’s next up in their research.

Ultimately, figuring out this mechanism will help correct bacterial dysbiosis by improving colonization of commensal bacteria…and of course, the health implications of that are vast.

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[i] G. P. Donaldson, M. S. Ladinsky, K. B. Yu, J. G. Sanders, B. B. Yoo, W. C. Chou, M. E. Conner, A. M. Earl, R. Knight, P. J. Bjorkman, S. K. Mazmanian. Gut microbiota utilize immunoglobulin A for mucosal colonization. Science, 2018; eaaq0926 DOI: 10.1126/science.aaq0926

 

[ii] https://www.sciencedaily.com/releases/2018/05/180504133624.htm