LAUSR

Abstract The DNA sensing pathway is a component of the innate immune system that recognizes DNA in the cytosol of cells. Its main purpose after DNA detection is to promote interferon production, which acts as a “warning signal” to neighboring cells and subsequently induces anti-viral and pro-inflammatory proteins. DNA that activates this pathway can originate from pathogens (herpes simplex virus, tuberculosis) or leakage from the nucleus (observed in cancer cells). Unfortunately, the regulatory factors underlying the DNA sensing pathway are poorly understood. Without a model describing the dynamics of the DNA sensing pathway, little progress can be made toward understanding its role with pathogens, cancer, and autoimmunity. To investigate the dynamics of the DNA sensing pathway, we constructed an ordinary differential equation (ODE) model parameterized from compiled literature data. With the established model, we performed several in silico knock-down experiments and observed sustained pathway activation without the presence of a negative feedback mechanism for DNA degradation and robustness to perturbations. This model provides a foundation to predict how pharmaceutical interventions could modulate the DNA sensing pathway to desired phenotypes.