MacDonald and Monteleone Science 307:1920, 2005
Imbalance of the commensal microbiota, called dysbiosis, is thought to be responsible for many of the host’s physical ills, including obesity, metabolic syndrome, inflammatory diseases, cancer, allergies, asthma, and autoimmunity. The relationship between the host immune system and the commensal microbiota is highly complex because these microbes possess many of the same traits as pathogenic microorganisms.
Hence, the immune system must co-exist with commensal microbiota and maintain a state of tolerance to self and innocuous environmental Ags, yet be able to vigorously repel invasion by a wide spectrum of pathogens. The various mechanisms operating here have yet to be clearly defined, but they probably converge and intertwine with each other indicating that our immune system needs to be viewed in the context of a super-organism.
How the host immune system interacts and establishes mutualism with the commensal microbiota is receiving increasing attention. Many of the pathogen recognition receptors involved in innate immunity are recognized as being at the forefront of the interaction with the commensal microbiota and are known to induce maturation of the mucosal immune system.
The highly conserved nature of such recognition is underscored by similar findings for the analogous receptors in Drosophila. The more important issue of how the immune system can distinguish between beneficial and pathogenic microbes is still largely a mystery. Such discrimination is likely to involve the adaptive immunity since this system, unlike the innate immune system, possesses a vast repertoire of highly specific Ag receptors.
This could be the reason why higher vertebrates possess a much more complex commensal microbiota that is 1-2 orders of magnitude higher in diversity than that in invertebrates, such as Drosophila, which does not have an adaptive immune system.
Our research projects are designed to study in depth the mammalian immune system, especially the adaptive system, in the context of the super-organism. All projects are designed to elucidate the role that commensal microbiota have on the development of the immune system, the changes the immune system undergoes in establishing and maintaining homeostasis with commensal microbiota, and on how commensal microbiota influence the host’s relationship with self and innocuous foreign Ags while maintaining reactivity to pathogenic microbes.