Figure 5

Differential expression of hypoxia, HIF-1α, and downstream effects in the central and peripheral regions of the necrotic granuloma. The central region of a necrotic granuloma is more hypoxic. As a result, there is greater HIF-1α expression with a panoply of downstream effects due to HIF-1 activity. One immune mechanism induced by HIF-1 is aerobic glycolysis, which in turn induces autophagy through the byproduct lactate. Hence, the central necrotic area of an intact human TB granuloma is usually sterile or with low bacterial burden. In contrast, the peripheral region of the granuloma less hypoxic with less HIF-1α induction. In the presence of macrophages that are less effective in killing Mtb (as shown by the foamy macrophages), there is less ability to kill Mtb, as shown by the greater bacilli number. However, in the presence of activated macrophages and T cells, the peripheral granuloma may also be efficient in either killing or controlling the Mtb infection. HIF-1α, hypoxia-inducible factor 1-alpha; IFNγ, interferon-gamma; Mtb, Mycobacterium tuberculosis; TB=tuberculosis;.