Portia Gough, Ph.D.

It is well known that the microbiome plays a role in almost every aspect of human physiology, yet much remains to be understood about the specific mechanisms of how commensal microbes affect human cellular function. The Host Microbe Symbiosis unit focuses on such mechanisms, with a particular focus on innate immune signaling and homeostasis at barrier sites such as the skin. Although the immune system likely expends most of its energy interacting with the multitude of organisms that occupy the human body, our knowledge of these interactions and how they influence the function of the immune system remains fairly limited. 

As allergic and autoimmune diseases and antibiotic-resistant infections become more common, it becomes increasingly necessary for us to better understand how commensal microbes shape immunity and homeostasis. The overarching principle of our research is that commensal organisms influence innate immune signaling at barrier sites via interactions with epithelial and immune cells and direct competition with pathogens. Therefore, understanding both the signaling between commensals and human cells and microbial interspecies interactions can lead to the development of targeted microbial therapeutics that reduce susceptibility to infection and maintain optimal function of barrier sites in the body. 

One such targeted microbial therapeutic is Roseomonas mucosa. This commensal skin bacteria was developed as a topical probiotic for atopic dermatitis by Dr. Ian Myles, also of the Laboratory of Clinical Immunology and Microbiology. R. mucosa serves as a model for how microbes can be used to effectively treat dysbiotic disease and restore optimal function to the skin, and it is the focus of our research thus far in the Host Microbe Symbiosis Unit. Our research is defining the mechanisms by which R. mucosa mediates immune regulation and supports homeostasis of the skin, particularly through its interaction with TLR5 and its bacteriostatic effects on Staphylococcus aureus. These studies provide a framework for future studies of other host-commensal interactions.  

The main techniques utilized in our study of host-commensal interactions are in vitro modeling with primary human cells, mouse models, quantitative proteomics, and various immunoassays to evaluate the interaction in three areas: initial contact of the microbe with host tissue (adhesion), downstream signaling from the activated receptor (e.g., TLR5), and the outcomes of the activated signaling pathway (cytokine, chemokine, antimicrobial peptide production, cell proliferation). A particular focus of the lab is that the downstream effects of interaction between commensal bacteria and TLRs appear to differ from the activation of TLRs by pathogen-derived ligands in a way that likely fine-tunes inflammatory responses for the host.