Identification of Key Processes that Control Tumor Necrosis Factor Availability in a Tuberculosis Granuloma
Figure 2
Schematic representation of the multi-scale two-compartment model of PPD bead granuloma and TNF-associated reactions.
(A) Binding interactions and reactions controlling TNF/TNFR dynamics at the single-cell level, including synthesis of TNFR1, TNFR2 and mTNF, sTNF release to the extracellular space under the effect of TACE activity, reversible binding of sTNF to TNFR1 and TNFR2, sTNF degradation, internalization of free and sTNF-bound TNFR1 and TNFR2, degradation of internalized TNFR1 and TNFR2, recycling of internalized TNFR1 and TNFR2, shedding of sTNF-bound TNFR2 and release of sTNF from the shed sTNF/TNFR2 complex. (B) TNF neutralization-associated reactions, including reversible binding of drug to mTNF and sTNF, release of drug-bound TNF from the membrane to the extracellular space and drug degradation. (C) Two-compartment model of granuloma that includes a bead of radius rbead surrounded by the inner compartment populated by macrophages and DCs and the outer compartment composed of lymphocytes. Numbers in (A) and (B) represent model reactions as listed in Table 2.