Disruption of interactions between host immune system and resident microbiota can have profound consequences for host health. As a result studying the role of immune system in regulating microbiota and the molecular mechanisms by which microbiota shape host immunity are currently a central question in the field of biomedical science.

Vaishnava lab focuses on following areas of research to gain a better understanding of complex and dynamic nature of host- microbe interaction at the intestinal mucosal surface:

1. Role of adaptive immunity in regulating host-microbe interaction.

Intestinal microbiota provides a strong selective pressure for the host to evolve adaptive immunity. However little is known about the adaptive immune mechanisms that work in concert with the innate immune effectors to maintain the physical separation of host and microbiota and limit subepithelial bacterial penetration. We are interested in studying the role of adaptive immunity in regulating composition and geographical location of the intestinal bacteria.

2. Bacteria regulated vitamin A metabolism.

Complex communities of bacteria inhabit the mammalian intestines that are continuously interacting with the host. These interactions play a critical role in shaping host immunity. Mechanisms by which intestinal bacteria guide the development of mucosal immune response are not well understood. A key factor in orchestrating mucosal immune responses in the intestine is retinoic acid (RA), a metabolite of vitamin A (retinol). Currently not much is known about whether and how bacteria regulate vitamin A metabolism in the intestinal mucosa. Our goal is to define the molecular mechanism by which gut bacteria modulate vitamin A metabolism in the intestine and how this regulates RAR signaling dependent immune function in the mucosal tissues.

3. Stratification of bacterial communities within the intestinal mucus layer. 

Intestinal bacteria play a critical role in regulating the metabolic potential of the host and greatly influences host biochemistry and susceptibility to disease. Moreover it has been shown that certain bacteria or their products exert powerful effects on immune cell differentiation whereas other species have no effect. The molecular basis for the differential ability of commensal species to trigger distinct immune developmental and metabolic pathways is yet to be determined. Our hypothesis is that this differential ability might be determined by the location of particular bacterial species with respect to the host epithelial surface. Our goal is to determine how bacterial communities are stratified within the intestinal lumen in order to better understand how they might influence host physiology and susceptibility to disease.

Molecular Microbiology and Immunology Department

Molecular and Cellular Biology