AUTHORS
ABSTRACT
Several facets of the host immune response to Salmonella infection have been studied independently at great depths to understand the progress and pathogenesis of Salmonella infection. The circumstances under which Salmonella infected individual succumbs to an active disease, evolves as a persister or clears the infection are not understood in detail. We have adopted a systems level approach to develop a continuous-time mechanistic model. We considered key interactions of the immune system state variables with Salmonella in mesenteric lymph node to determine the final disease outcome deterministically and exclusively temporally. The model accurately predicts the disease outcomes and immune response trajectories operational during typhoid. The results of the simulation confirm the role of anti-inflammatory (M2) macrophages as a site for persistence and relapsing infection. Global sensitivity analysis highlights the importance of both, bacterial and host attributes in influencing the disease outcome. It also illustrates the importance of robust phagocytic and antimicrobial potential of M1 macrophages and dendritic cells in controlling the disease. Finally, we propose therapeutic strategies for both antibiotic sensitive and resistance strains (like IFN-γ therapy, DC transfer and stimulate phagocytic potential). Likewise, we suggest prevention strategies like improving the humoral response and macrophage carrying capacity that could complement current vaccination schemes for enhanced efficiency.
Click here to read the article, published in International Immunology.
