Figure 1
Morphological features of apoptosis, necroptosis, and pyroptosis and their linkages with immunogenicity. (A) Dying cells revealed by scanning electron microscopy. In RAW264.7 cells, apoptosis was induced by TNF+Smac mimetics; necroptosis was induced by TNF+Smac mimetics+zVAD; pyroptosis was induced by LPS priming followed by nigericin treatment. (B) Membrane blebbing followed by formation of apoptotic bodies is commonly observed in apoptosis. Under certain conditions, such as inhibition of PANX1 by trovafloxacin or further combined inhibition of actomyosin contraction by cytochalasin D or GSK 269962, apoptotic cells exhibit two apoptotic body-related morphological changes called apoptopodia and 'beads-on-a-string' protrusions. These membrane-enveloped fragments can be immunogenic, non-immunogenic, or even immunosuppressive under different experimental settings. However, the regulated secondary necrosis of apoptotic cells mediated by DFNA5 can be highly inflammatory. In necroptosis, MLKL-mediated plasma membrane rupture leads to release of cellular contents and thus immunogenicity. Pyroptosis results from an inflammatory response induced by inflammasome activation, which is frequently observed in professional phagocytes and tightly associated with IL-1β/IL-18 secretion. Whether GSDMD-mediated pyroptosis itself is immunogenic awaits further investigation.
