Fig 2: Calibrated HostSim recapitulates dynamics of Mtb infection at both granuloma-scale and host-scale.

(A) Snapshot of HostSim time-lapse video showing virtual lungs, granulomas, lung draining lymph nodes, and blood cell concentrations for three cell types. Mtb-specific effector, effector memory and central memory T cells numbers within blood are qualitatively captured by a color change across time, from black (very few cells in the blood) to bright red (representing the maximum number of cells of that blood type across the simulation). At day 70, Mtb-specific effector T cells numbers peak, Mtb-specific effector memory T cells are continuing to grow in magnitude, and Mtb-specific central memory T cells have not yet started to differentiate in large numbers. As time progresses, more memory T cells will differentiate and be present within the blood compartment. Full time-lapse videos can be found at http://malthus.micro.med.umich.edu/lab/movies/HostSim/. We calibrated HostSim to published datasets from NHPs on (B) lung granuloma CFU, macrophage and T cell granuloma numbers from previous studies (26). These datapoints come from separate studies and the granuloma dataset is richer than the cellular datasets. (C) blood CD4+ T cell data and (D) blood CD8+ T cell data from both simulation and NHP following a single infection event in NHP studies (25,26,64,65). Published NHP study data are shown as black dots across the graphs. For direct comparison, we display simulation data as gray (granuloma outcomes) or red (blood outcomes) clouds that outlines the 1^st and 99^th percentile across 500 host simulations. Gray and red lines represent the medians of those simulations. Simulations plotted show from day of infection until day 200 post-infection.