Table A1.

Parameters used for wide parameter sweep

Symbol	Parameter name	Value or range	Units
Mtb parameters
α1	Growth rate intracellular Mtb	1.003	cells
α2	Growth rate extracellular Mtb	1.001	cells
α3	Death rate of extracellular Mtb in caseum	1.5	cells
Core model parameters
γ1	Diffusion time step	60	seconds
γ2	Molecular time step	6	seconds
γ3	Diffusion smoother time step	1.2	seconds
γ4	Number of smoother steps	0	n/a
γ5	Number of host cells causing caseation	10	n/a
γ6	Time to heal caseation	[1642, 2462]	days
γ7	Threshold for TNFα induced apoptosis	[1393, 2089]	molecules
γ8	Rate of TNFα induced apoptosis	[1.17e–6, 1.76e–6]	1/seconds
γ9	Minimum number chemokine molecules	[0.514, 0.77]	molecules
γ10	Saturating number of chemokine molecules	[374, 562]	molecules
γ11	Diffusivity of TNFα	5.2e–8	cm2/s
γ12	Diffusivity of IL10	5.2e–8	cm2/s
γ13	Diffusivity of active TGF-β1	5.2e–8	cm2/s
γ14	Diffusivity of chemokines	5.2e–8	cm2/s
γ15	Degradation rate of TNFα	0.00158	molecules/molecular time step
γ16	Degradation rate of IL10	0.00048	molecules/molecular time step
γ17	Degradation rate of inactive TGF-β1	[9.28e-6, 1.39e–5]	molecules/molecular time step
γ18	Degradation rate of active TGF-β1	[8.0e-4, 0.0012]	molecules/molecular time step
Macrophage parameters
μ1	Fraction of grid compartments with a macrophage	[0.024, 0.036]	n/a
μ2	Number of time steps before a resting macrophage can move	2	n/a
μ3	Number of time steps before an activated macrophage can move	16	n/a
μ4	Number of time steps before an infected macrophage can move	[112, 168]	n/a
μ5	Synthesis rate of TNFα	1.5	molecules/diffusion time step
μ6	Synthesis rate of CCL2	6	molecules/diffusion time step
μ7	Synthesis rate of CCL5	6	molecules/diffusion time step
μ8	Synthesis rate of CCL9	12	molecules/diffusion time step
μ9	Synthesis rate of IL10 by an activated macrophage	0.3	molecules/diffusion time step
μ10	Synthesis rate of IL10 by and infected macrophage	0.02	molecules/diffusion time step
μ11	Synthesis rate of Inactive TGF-β1 by macrophages	[0.0001, 0.01]	molecules/diffusion time step
μ12	Number of bacteria a resting macrophage can phagocytose	1	n/a
μ13	Probability of resting macrophage killing bacteria	[0.23, 0.35]	n/a
μ14	Threshold for intracellular bacteria causing chronically infected macrophages	[8,12]	bacteria
μ15	Threshold for intracellular bacteria causing macrophage to burst	[13, 20]	bacteria
μ16	Number of bacteria an activated macrophage can phagocytose	[4, 6]	n/a
μ17	Fraction of inactive TGF-β1 activated by a mac	[1e–6, 1]	n/a
μ18	Amount of TGF-β1 that inhibits macrophages	[1e–6, 1]	molecules
μ19	Fraction of active TGF-β1 in a compartment bound by a mac	[1e–6, 1]	n/a
μ20	Probability of an activated macrophage healing a caseated compartment in its Moore neighborhood	[0.0128, 0.0129]	n/a
T cell parameters
τ1	Probability of a T cell moving to the same compartment as a macrophage	[0.05, 0.08]	n/a
τ2	Probability of a T cell moving to the same compartment as a T cell	0.08	n/a
τ3	Synthesis rate of TNFα by IFNγ-producing T-cell	0.15	molecules/diffusion time step
τ4	IFNγ-producing T-cell probability of inducing Fas/FasL mediated apoptosis	[0.0152, 0.0228]	n/a
τ5	Probability of IFNγ-producing T-cell to secrete TNFα	[0.048, 0.072]	n/a
τ6	Probability of IFNγ-producing T-cell to secrete TNFα	[0.288, 0.432]	n/a
τ7	Synthesis rate of TNFα by cytotoxic T-cell	0.015	molecules/diffusion time step
τ8	Probability of a cytotoxic T-cell killing a macrophage	[0.012, 0.18]	n/a
τ9	Probability of a cytotoxic T-cell killing a macrophage and all associated Mtb	[0.61, 0.91]	n/a
τ10	Probability of cytotoxic T-cell to secrete TNFα	[0.056, 0.084]	n/a
τ11	Synthesis rate of IL10 by regulatory Tcell	0.739	molecules/diffusion time step
τ12	Synthesis rate of TGF-β1 by regulatory T cell	[0.0001, 0.01]	molecules/diffusion time step
τ13	Probability a regulatory T cell will deactivate an activated macrophage	[0.011, 0.016]	n/a
τ14	Bound TGF-β1 that inhibits T cells	[0.04, 0.2]	molecules
τ15	Fraction of active TGF-β1 in a compartment bound by a T cell	[1e–4, 0.2]	n/a
Fibroblast Parameters
ζ1	Maximum fibroblast age 28800 agent timesteps ζ2 Initial number of fibroblasts in a simulation	50	n/a
ζ3	Probability a fibroblast will move	[0.001, 0.5]	n/a
ζ4	Synthesis rate of TGF-β1 by a fibroblast	[0.001, 0.1]	molecules/diffusion time step
ζ5	Units of αSMA synthesized per TGF-β1 binding event	1e–10	n/a
ζ6	Time until a fibroblast can attempt to proliferate	[24, 48]	hours
ζ7	Bound molecules of IL10 that inhibits fibroblast proliferation/differentiation	[1e4, 2e4]	molecules
ζ8	TGF-β1 myofibroblast differentiation threshold	[2.0e–7, 8.0e-7]	molecules
ζ9	TGF-β1 fibroblast proliferation threshold	[2.0e–7, 8.0e-7]	molecules
ζ10	Minimum ratio of TGF-β1 to IL10 required for myofibroblast differentiation	[1e–11, 1e–9]	n/a
ζ11	TNFα fibroblast proliferation/differentiation threshold	[0.025, 0.5]	molecules
ζ12	Synthesis rate of Il10 by fibroblast	[3.48e–22, 3.48e–16]	molecules/molecular time step
ζ13	Binding rate of Il10 by fibroblast	[1e–12, 1e–8]	molecules/molecular time step
ζ14	Fibroblast sensitivity to Il10	[0.001, 10]	n/a
ζ15	Fibroblast sensitivity to TGF-β1	[0.000001, 0.1]	n/a
ζ16	Probability of a fibroblast differentiating into a myofibroblast	[0.1, 5.0]	n/a
Myofibroblast Parameters
ω1	Collagen synthesis rate	[1e–7, 1e–5]	molecules/agent time step
ω2	Probability of apoptosis	[0.002, 0.2]	n/a
ω3	αSMA degradation rate	[0.001, 10]	molecules/molecular time step
ω4	αSMA synthesis rate	[1e–10]	molecules/molecular time step
Recruitment Parameters
ρ1	Maximum macrophage recruitment probability	[0.112, 0.168]	n/a
ρ2	Maximum IFNγ-producing T cell recruitment probability	[0.112, 0.168]	n/a
ρ3	Maximum cytotoxic T cell recruitment probability	[0.079, 0.12]	n/a
ρ4	Maximum regulatory T cell recruitment probability	[0.0232, 0.0348]	n/a