Journal Club: Immunology/Microbiota

Graduate Division

Presentation: “Spare the bacillus, spoil the child: The microbiome limits iNKT cell numbers and protects against IBD and asthma.”

Presenter: Emily Bradford

Paper: Olszak T., et al. Microbial exposure during early life has persistent effects on natural killer T-cell function. Science, 2012 Apr 27;336(6080):489-93.

In a nutshell:

A hot topic in the immunology world these days is the hygiene hypothesis, the idea that early exposure to more bacteria is beneficial to adult health.

This is linked to the observation that developed countries have seen an increased incidence of allergic diseases, such as asthma, and autoimmune diseases, such as inflammatory bowel disease (IBD). Furthermore, scientists have noted the lack of proper immune development in germ-free (GF) mice that have been maintained in sterile conditions and do not have a microbiome. Why might a diverse microbiota influence how our adult immune systems behave?

On a cellular level, we have observed that invariable natural killer T (iNKT) cells can cause inflammatory disease in response to bacterial exposure.  These cells have receptors that bind bacterial antigens, which are molecules on bacteria that evoke an immune response. This response is the production of cytokines such as IL-4 and IL-13.

Cytokines are proteins that tell the immune system what to do, and these in particular are associated with allergic and inflammatory responses.  With this in mind, the authors of this paper wondered if the microbiome influenced immune response through iNKT cells.  If you lack microbiota, do you have more disease-causing iNKT cells?

The authors found that yes, GF mice lacking a microbiome had more iNKT cells in their organs of disease (that is, lungs in the case of asthma, and the gut in the case of IBD) when compared with specific pathogen-free (SPF) mice that had been maintained in non-sterile conditions and had an intact microbiome. Moreover, the GF mice had more severe disease and lower survival rates.  To confirm that this was actually a result of the differences in iNKT cell populations, the authors blocked the function of iNKT cells, and this prevented death of the GF mice.  Based on these findings, the authors proposed a model in which a diverse microbiota prevents the development or survival of disease-causing iNKT cells.

Now, it’s great that we now know how bacterial exposure might prevent adult disease, but this doesn’t help us get rid of asthma or IBD.  How can we use this therapeutically?  To this end, the authors wanted to know if colonizing adults with a more diverse microbiome might help treat disease.  They colonized GF neonates and adults with bacteria and compared their responses to disease.  Ultimately, they found that while exposure to bacteria was able to improve the outcomes for neonates,  it was too late for the adults.  So, parents, maybe it’s a good idea to let your kids eat those cookies they dropped on the floor.