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Applied
Math Seminar |
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A key issue for the study of tuberculosis infection (TB) is to understand why individuals infected with Mycobacterium tuberculosis experience different clinical outcomes. Elaborating the immune mechanisms that determine whether an infected individual will suffer active TB or latent infection can aid in developing treatment and prevention strategies. To better understand the dynamics of M. tuberculosis infection and immunity, we have developed a virtual model based on a system of nonlinear, ordinary differential equations that qualitatively and quantitatively characterizes the cellular and cytokine control network operational during TB infection. Using this model we identify bifurcation parameters that govern key regulatory elements in the host response. The model indicates, however, that even if latency is achieved, it may come at the expense of tissue damage if the response is not properly regulated. A balance in TH_1 and TH_2 immune responses governed by IFN-$\gamma$, IL-10, and IL-4 facilitate this downregulation. These results are further explored through virtual deletion and depletion experiments. |