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An online supplement for Neutrophil dynamics affect Mycobacterium tuberculosis granuloma outcomes and dissemination |
[ Kirschner Lab Time-Lapse Simulations Homepage ]
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Time-lapse videos corresponding to Figure 3 snapshots in main paper. These are 6 different simulations of granulomas including neutrophils and showing different outcomes. Click on the individual video links below for additional details. GranSim produces simulated granulomas that reflect granulomas in experimentally-infected macaques. | |
 Video 3A |
 Video 3B |
 Video 3C |
 Video 3D |
 Video 3E |
 Video 3F |
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Dissemination time-lapse videos corresponding to Figure 7A snapshot in main paper. GranSim produces simulated granulomas that reflect granulomas undergoing dissemination in experimentally-infected macaques. These three videos highlight different timeframes post-infection during the evolution of a sample neutrophil-facilitated dissemination of a granuloma. Click on the video links below for additional details. | |
 Video 7A |
 Video 7B |
 Video 7C | |
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| Supplement Figure 1: Overview of the fundamental rules governing neutrophil behavior in the model. We distinguish among cell types using the following color scheme: neutrophils (purple), macrophages (green -- any type, orange -- infected, red -- chronically infected), T cells (pink -- any type), extracellular Mtb (brown). Due to space limitations in figure, note that intracellular Mtb and extracellular Mtb are occasionally abbreviated as “intMtb” and “extMtb”, respectively. | |
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| Supplement Figure 2: Spatial outcomes for virtual neutrophil deletion and depletion studies. Simulated granulomas at day 200 PI. A) As a wild-type control, we use a simulated granuloma that has medium levels of CFU and abundant levels of neutrophils at 200 days PI. Panels B-F are the virtual deletion and depletions using this same granuloma set. B) Neutrophil deletion. Neutrophils are not present on the grid at any point during the simulation. C-F) Virtual neutrophil depletion at days 25, 50, 75, and 100 PI, respectively. Here, we use a color scheme that distinguishes among the different simulated cell types: Macrophages (green-- resting, orange-- infected, red-- chronically infected, blue-- activated), Neutrophils (purple), T cells (Tgam-- pink, Tcyt-- maroon, Treg-- cyan), extracellular Mtb (brown), and caseum (beige) are shown. | |
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| Supplement Figure 3: Temporal outcomes for virtual neutrophil deletion and depletion studies. Panels A-C show temporal simulated data for the six virtual experiments (control, neutrophil deletion, and four temporally-distinct neutrophil depletions). Each simulated data set contains 25 granulomas. The color key is shown in Panel B. Panel A: CFU versus days PI. Red = experimental data from NHPs. We observe that deleting or depleting neutrophils increases total CFU at day 200 PI in most cases, especially when depletion occurs by day 50. Panel B: Neutrophil cell counts versus days PI are shown. Neutrophil count quickly goes to zero following neutrophil depletion. Panel C: We observe that deleting or depleting neutrophils at day 25 PI increases granuloma diameters at day 200 PI. Panel D: Using the control parameter set, we varied the time PI of neutrophil depletion. Reduced CFU at day 200 generally correlates with later neutrophil depletion PI. Depleting neutrophils between days 50 and 200 has comparable effects on CFU at day 200. | |
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| Supplement Figure 4: Spatial outcomes for virtual neutrophil deletion and depletion studies. Simulated granulomas at day 200 PI. A) As a wild-type control, we use a simulated granuloma that has low levels of CFU and abundant levels of neutrophils at 200 days PI. Panels B-F are the virtual deletion and depletions using this same granuloma set. B) Neutrophil deletion. Neutrophils are not present on the grid at any point during the simulation. C-F) Virtual neutrophil depletion at days 25, 50, 75, and 100 PI, respectively. At the time of depletion, all future neutrophil recruitment is prohibited. Here, we use a color scheme that distinguishes among the different simulated cell types: Macrophages (green-- resting, orange-- infected, red-- chronically infected, blue-- activated), Neutrophils (purple), T cells (Tgam-- pink, Tcyt-- maroon, Treg-- cyan), extracellular Mtb (brown), and caseum (beige) are shown. | |
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| Supplement Figure 5: Temporal outcomes for virtual neutrophil deletion and depletion studies. Panels A-C show temporal simulated data for the six virtual experiments (control, neutrophil deletion, and four temporally-distinct neutrophil depletions). Each simulated data set contains 25 granulomas. The color key is shown in Panel B. Panel A: CFU versus days PI. Red = experimental data from NHPs. We observe that deleting or depleting neutrophils increases total CFU at day 200 PI in all cases. Panel B: Neutrophil cell counts versus days PI are shown. Neutrophil count quickly goes to zero following neutrophil depletion. Panel C: We observe that deleting or depleting neutrophils increases granuloma diameters at day 200 PI. Panel D: Using the control parameter set, we varied the time PI of neutrophil depletion. At day 200, reduced CFU correlates with later neutrophil depletion PI. | |
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| Supplement Table 1: | Supplemental table of all varied GranSim parameters, not including neutrophil parameters. The symbol * denotes parameters that were sampled using a log uniform distribution rather than the default uniform distribution. |
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| Description of GranSim rules: | Rules for GranSim without Neutrophil |
| [ Kirschner Lab Time-Lapse Simulations Homepage ] |