Fig. 2.

Proposed scheme for different forms of cell death. Apoptosis and necrosis apparently are the most distinct forms of cells death. Apoptosis is a strictly regulated process of cell death in which cells undergo some modifications that permits their silent removal by adjacent cells. These modifications include reduction of cell volume and packaging of cellular contents, DNA and nuclear fragmentation, formation of cytoplasmic and membrane blebs, and phosphatidylserine externalization. In contrast, necrotic cells increase their volume and lose the cell membrane integrity leading to the release of their cellular contents and consequent inflammation. Note that necrotic cells preserve the uncondensed DNA content. Autophagy and pyroptosis could be seen as another polarized scheme of cell death, since they have opposite consequences to the immune response. Like necrosis, pyroptosis is a highly inflammatory process in which cells also lose their cell membrane integrity. However, along with cellular contents, pyroptotic cells secrete inflammatory cytokines such as IL-1β, IL-18, and IL-33. Interestingly, the nuclear modifications observed during pyroptosis are similar to the DNA fragmentation and nuclear condensation detected in apoptosis. Similarly to apoptosis, autophagy is another silent process by which cells can undergo death. In this case, cells maintain the membrane integrity and exhibit a profound vacuolization as a result of the double-membrane composed autophagosome formation. Since autophagy and pyroptosis share some molecular characteristics with both apoptosis and necrosis, we inserted this new scheme in the middle of them. Moreover, as TLR clearly modulate autophagy and inflammasomes are the key inducers of pyroptosis, these two families of PRR are represented in cells undergoing their respective forms of cell death