Host-microbe interactions in the gastrointestinal tract and their contributions to chronic inflammatory responses

My project involves researching host-microbe interactions in the gastrointestinal tract and their contributions to chronic inflammatory responses. There are two "arms" to my project. In one arm, I will study "TIGER" cell populations (T cells - Innate-like Gut-Enriched and Resident), aiming both to outline new subsets and to better characterise the subsets already discovered. The second arm of my project relates to an investigation of cytomegalovirus (CMV) as a potential driver of immune-mediated disease in the gastrointestinal tract.


"TIGER" cells express a high level of the marker CD161, traditionally an NK cell marker. However, their physiologic responses are what render TIGER cells truly distinct from "conventional" T cells. Whilst conventional T cells require peptides to be presented on molecules of the major histocompatibility complex (MHC), CD161-high cells are "commensal-reactive" meaning that they can become activated by non-peptide bacterial derivatives in the absence of MHC. Gut-resident CD161-high cells therefore detect and respond to the gastrointestinal microbiota in an important manner. More unconventional still, these cells are similar to innate immune cells and referred to as "innate-like" in their capacity to respond to the cytokines IL-18 and IL-21. Sensitivity to a range of inflammatory stimuli has proposed CD161 high cells as key amplifiers of inflammatory responses in host defense against bacteria and viruses; most recently, CD161-high mucosal-associated invariant T (MAIT) cells were outlined as key players in SARS-CoV-2 infection outcomes. My research aims to continue characterisation of these cell populations, particularly the factors that trigger activation of their newly defined tissue repair capacities.


The second arm of my project refers to outlining whether CMV acts as an inflammatory driver in Crohn's disease and ulcerative colitis, part of a family of immune-mediated diseases referred to as inflammatory bowel disease (IBD). Whilst commonplace in the general population, CMV infection in IBD sufferers can be associated with severe clinical presentations. CMV infection itself can trigger gastrointestinal inflammation (colitis), which is challenging to distinguish from underlying IBD flares. My research will use transcriptional and proteomic approaches to characterise the mechanisms by which CMV may be acting as an inflammatory driver in IBD, with the aim of proposing potential treatment targets for CMV-positive IBD patients.