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. Author manuscript; available in PMC: 2009 Feb 1.
Published in final edited form as: Cell Microbiol. 2007 Sep 10;10(2):332–343. doi: 10.1111/j.1462-5822.2007.01044.x

Figure 6. A model of LT-induced macrophage death.

Figure 6

Following entry into cells, LF is released from late endosomes and cleaves the MEK proteins in the cytosol (20-40 min) in both LTsensitive and resistant macrophages. In a series of unknown events, possibly involving the cleavage of additional LF substrates, downstream effects of MEK inactivation or direct involvement of the sensitive allele of Nalp1b, LF induces increases in plasma membrane permeability, resulting in ion fluxes in LT-sensitive, but not resistant cells. These ion fluxes are sensed by functional Nalps in the macrophage, possibly including Nalp1b, and lead to caspase-1 recruitment, inflammasome formation, and caspase-1 activation (50-60 min) in sensitive cells only. Active proteasomes are required in an unknown step that precedes caspase-1 activation. Caspase-1 activity is then required in unknown late events that lead to cell lysis. In a pathway not required for cell death, caspase-1 cleaves IL-1β and IL-18, and the mature forms of the cytokines are subsequently released.