Figure 2.

Kinetics of combined units and corresponding transition rate values of the spon-IE model and the PMNmed-IE model. Experimental data from whole-blood infection assays (dashed lines) with corresponding SDs are compared to the simulated data (solid lines) by the spon-IE model (left column) and the PMNmed-IE model (middle column). The thickness of solid lines indicates the mean ± SD of 50 simulations with transition rate values that were randomly sampled within their corresponding SD. Mean values (data points) and SDs (error bars) of transition rates (right column) were quantified by the global parameter estimation algorithm Simulated Annealing based on Metropolis Monte Carlo scheme for the spon-IE model (black data points) and PMNmed-IE model (gray data points). The transition rates are given by the phagocytosis rate ϕ_N of PMN and the phagocytosis rate ϕ_M of monocytes, the intracellular killing rates κ_M and κ_N of both monocytes and PMN, the transition rates γ and ${\overline{\kappa }}_{EK}$ which define the extracellular killing, and the spontaneous immune-evasion rate ρ and the PMN-mediated immune-evasion rates $\overline{\mathrm{\rho }}$ and γ_R, respectively. The time-course of the relative number of killed pathogens (P_K), which are indicated by red dashed lines, were experimentally measured by survival assays. The relative number of fungal cells that were associated with monocytes (P_M), PMN (P_N), or in extracellular space (P_E) were measured by association assays and indicated by orange, blue, or green dashed lines, respectively. The experimental results were compared with the corresponding combined units calculated for the simulated data. Black solid lines refer to the simulated time-course of immune-evasive fungal cells (P_IE). Kinetics of a Candida albicans infection simulated by (A) the spon-IE model and (B) the PMNmed-IE model. (C) Transition rates quantified by both models for a C. albicans infection. Kinetics of a Candida glabrata infection simulated by (D) the spon-IE model and (E) the PMNmed-IE model. (F) Transition rates quantified by both models for a C. glabrata infection.