Program
| MSD6d | |
|---|---|
| Simenone Marino | |
| Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michiga | |
| Title | A multi-compartmental model of Mycobacterium tuberculosis infection in mice: the role of antigen dose in T cell priming |
| Abstract | Infection with Mycobacterium tuberculosis (Mtb) induces a host cellular immune response capable of recognizing mycobacterial antigens, that leads to the production of type I cytokines, activating infected macrophages that kill or at least contain the bacterial infection. T cell priming (CD4+ and CD8+ T cells) that occurs in the lymph node is key to the successful development of a protective adaptive immunity and host resistance to Mtb infection. Once primed, these cells circulate to the lung to participate in the local immune response there. In an effort to understand these complex series of events including the involvement of multiple T cell subsets, we developed a mathematical model. Our goal was to elucidate which mechanisms are affecting T cell priming in Mtb infection and whether or not antigen dose plays any role in the quality of priming of T cells. Our non-linear ordinary differential equations system comprises two main physiological compartments (lung and lymph node), each one populated with different cell populations (macrophages, dendritic cells and lymphocytes), bacteria and cytokines. Mouse data from aerosol infection in respiratory chambers have been collected and extensively used to calibrate the model, which will be discussed. Model fitting and sensitivity analysis results inform us regarding similarities and differences between lung and lymph node biological mechanisms, as well as if and how antigen dose plays a role in T cell immunity. Key mechanisms are targets for designing vaccine or adjunctive treatment strategies. |
| Location | Woodward 6 |