The innate immune system provides the first line of defense against infection. An innate immune response is started when toll-like receptors (TLRs), which are expressed by many cells of the immune system including macrophages and dendritic cells, bind conserved bacterial components like lipopolysaccharide or flagella. This triggers signaling cascades that result production of cytokines important in controlling the infection. It also initiates production of chemokines that recruit various cell types to the infected tissue. In addition, TLR signaling induces dendritic cell maturation, a process that transforms them into cells uniquely capable of activating naïve T cells to start a specific immune response. Thus, TLR signaling triggers innate immunity and induces long term, specific immunity to the infection.
The group focuses on the response of dendritic cells and monocytes/macrophages to oral infection with Salmonella and Listeria. We aim to decipher the TLR signaling pathways involved in inducing dendritic cell maturation and T cell function during infection with these bacteria. The role of distinct dendritic cell subsets, as well as the mechanisms driving recruitment and activation of dendritic cells and monocytes during infection, is also studied. The project allows us to understand both the bacterial and host factors required to recruit and activate the cells that initiate immunity to these intracellular pathogens.
Another project involves examining how dysfunctional recognition of intestinal flora by immune cells, particularly dendritic cells, contributes to the etiology of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. This is done using an experimental model where intestinal mucin is lacking. In this way we can study the events that initiate and perpetuate chronic intestinal inflammation. An additional approach to understanding what drives inflammatory bowel diseases involves studying dendritic cell and macrophages from the intestine of patients with Crohn's disease or ulcerative colitis. The aim of these patient studies is to characterize possibly aberrant reactivity of intestinal dendritic cells and macrophages towards bacteria that may contribute to the disease.