My group is using multi-photon microscopy (MPM) in combination with histological and genetic approaches to study the immune response to bacterial infection in the spleen. The spleen plays a crucial role in host defense by trapping and destroying blood-borne pathogens and triggering the adaptive immune response. However, few details are known regarding how early host-pathogen interactions lead to antigen presentation and immunity. Preliminary results from my lab indicate that bacterial challenge in mice induces the rapid redistribution of splenic macrophages and dendritic cells in a bacteria-specific fashion. Our hypothesis is that tissue remodeling serves an “antigen transport” function that delivers pathogen-derived antigens to distinct microenvironments for presentation. Because both the antigen presenting cell type and the local environment impact the immune response, this could provide a mechanism to tailor immune responses to a wide-range of pathogens. We are focusing our investigations on three key stages of infection: 1) the initial capture and fate of bacteria in marginal zone macrophages and dendritic cells, 2) the migration of these cells in response to infection, and 3) bacterial-antigen presentation in tissue microenvironments and its influence on the subsequent adaptive immune response. Moreover, the multi-dimensional cell tracking data from these studies is being used to create in silico models of infection and immunity in the hope of providing fresh mechanistic insight into microbial pathogenesis and guide vaccine development.

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