A Spotlight on Liquefaction: Evidence from Clinical Settings and Experimental Models in Tuberculosis

Figure 1

Interactions between the factors involved in the liquefaction process. The colour of the arrows shows the ability to induce a process (in gray) or inhibit it (in red), and the thickness of the arrow is proportional to the intensity of this induction. The upper lobe appears to be the sine qua non condition for the process to take place. Macrophage (MΦ) activation and the presence of CD4 is linked to the appearance of different cytokines with time: TNF initially, followed by IFN-γ and IL-4, and TGF-β from the onset and peaking at the chronic phase. All those cytokines are profibrotic (in violet) except for IFN-γ (in yellow). This site mainly undergoes a profibrotic process although there is also a nonspecific antifibrotic effect arising from the macrophages and their enzymatic activity. Extracellular bacilli also have antifibrotic activity and promote macrophage activation although they are also thought to inhibit such activation to some extent. Fibrosis prevents liquefaction whereas liquefaction is promoted by macrophages, the immune response, by promoting the apoptosis of infected macrophages, and extracellular bacilli. Liquefaction induces cavitation, inhibits macrophage activation (indeed, it appears to destroy them), and promotes extracellular bacillary growth. Overall, liquefaction comes first, and then the extracellular multiplication of bacilli occurs. Fibrosis, and thus resume of the liquefaction, would occur only after the number of extracellular bacilli is reduced sufficiently to allow attempts at healing to take place. Finally, a large number of extracellular bacilli results in tissue destruction, cavity formation, and the death of the macrophages that attempt to inhibit such bacillary growth.