Dr. Yasmine Belkaid of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), is chief of the Mucosal Immunology section and co-director of the trans-NIH metaorganisms initiative. Her work explores mechanisms at barrier sites (i.e. skin and gut) that regulate immune responses to pathogens.
Belkaid presented a talk at the recent Keystone Symposium called, “Compartmentalized Control of Tissue Immunity by Commensals”, which included updates on other work in her lab. She took a moment at the conference to answer some questions for the GMFH editors.
Can bacteria that are no longer present in the body still affect health?
We have to take into account the fact that, especially in Westernized countries, we have a huge [number] of acute infections. And these acute infections are representing very strong challenges for the immune system — it has to rebound from [them] constantly. So what we are interested to explore is how certain infections may disrupt the relationship with the microbiota, but also may potentially remodel the immune system, and how together, those changes in the microbiota and the immune system could have long-term consequences.
How might antibiotics affect physiologically normal states of inflammation?
When we refer to inflammation, usually we refer to pathogenic inflammation. We need to remember there is what we refer to as ‘constitutive homeostatic inflammation’. That’s going to be, for example, what happens in the [gastrointestinal] tract, in which the microbes are constantly ‘tickling’ the system and creating a low-grade inflammation that is physiological[ly normal].
This inflammation is very important because [it] allows the control of pathogens; it allows the control of repair mechanisms… so if you remove the microbiota steady states, do you actually remove this physiological inflammation that is required for the immune system?
I think removing these microbes [via antibiotics] is going to remove all this constant inflammation that is absolutely required. And actually, experimentally it has been done. If you remove the microbiota, you prevent the capacity of the host to mount adaptive immunity to pathogens. So this constant low-grade inflammation is required in the immune system.
What are the clinical implications of current research on the microbiota and immunity?
I think what we need to understand is actually how microbes are capable [of creating] and stimulat[ing] the immune system in a way that is non-inflammatory, which is really what they do. The clinical implication is [that] we’re going to understand the physiological interaction between… microbes and the immune system, and we’re going to be able to utilize therapeutic strategies that can actually allow the control of pathogens without creating tissue damage.
The microbes are going to ‘teach’ us how to create the therapies that are perfectly well-balanced to preserve tissue integrity. It could be microbiome therapeutics, it could be probiotics, [or] it could be also using some of the ligands or metabolites. I think we have evidence, during this meeting, that some of them can actually replace the microbe itself. So I think we’re going to learn about all the different mechanisms by which to manipulate the immune system — the balance between regulation and inflammation [that microbes] are creating — and we’re going to be able to tune the response in the direction we want.
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