Journal Club: Immunology/Microbiota

Thursday, October 18, 2012

Presentation: “‘Are We Exclusive?’ A host-specific microbiota appears to be critical for mammalian immune maturation.”

Presenter: Katherine Farrar (2nd year BMS student)

Paper: Chung H, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012 Jun 22;149(7):1578-93.

In a nutshell:

Lately, the biomedical research world has been hearing a lot about gut microbiota.  We mammals are home to tons of bacteria—in fact, we’re made up of more bacteria than mammalian cells, and lots of these reside in the gut.  That might sound kind of scary, given what we know about harmful disease-causing bacteria, but in truth we host a lot of commensal bacteria.  These gut commensals obtain nutrients from us as we digest our food, and in return, they help us digest that food. These days, we’re finding that they also perform other crucial roles. 

One of these roles seems to be facilitating development of our immune systems.  Several research groups have found that our harmless microbiota may actually be helping us fight off other disease-causing bacteria and viruses.  Scientists have noticed, for instance, that germ-free mice, raised and maintained in sterile conditions throughout their lives, are immune-deficient. 

Based on this observation, the authors of this Cell paper wanted to test the connection between microbiota composition and immune development.  Specifically, they wanted to know if microbiota from another species, such as humans, would lead to normal immune development in mice.

To test this, the authors fed mice microbiota from mice (MMb) or humans (HMb).  The MMb and HMb mice had the same number of commensal bacteria but different immune profiles. Specifically, their ratios of different helper T-cell subtypes differed, which can influence the balance between overactive immunity and immune suppression, and the HMb mice were immune-deficient. As further proof of principle, when MMb and HMb mice were infected with salmonella to test their immune function, MMb but not HMb mice were able to fight off the infection.  (You might be thinking, “Wait, mice and humans are pretty different!” The authors also tested microbiota from rats, which are a bit more closely related to mice.  There was no significant difference between mice fed microbiota from humans or mice.<rats?>)

Ultimately, only the MMb mice fed mouse-specific microbiota were able to develop a normal immune system.  The authors thus concluded that gut microbiota are species-specific, and that only the microbiota from the same host species is able to promote normal immune development.