Cell-Cycle Regulators and Cell Death in Immunity

Abstract

Various cell death mechanisms are integral to host defense in both plants and mammals. Plant defense against biotrophic pathogens is associated with programmed cell death (PCD) of the infected cell. This effector-triggered PCD is partly analogous to pyroptosis, an inflammatory host cell death process that plays a crucial role in defense against microbial infections in mammals. Plant effector-triggered PCD also shares with mammalian apoptosis the involvement of cell-cycle regulators as signaling components. Here we explore the similarities between these different cell death programs as they relate to host defense and their relationship to the cell cycle.

Figure 1. Diagram of relevant similarities and differences between plant effector-triggered PCD (left) mammalian pyroptosis (center) and mammalian apoptosis (right)

In plants, effector-triggered PCD is initiated by NB-LRR-mediated perception of the presence of specific intracellular effectors secreted by pathogens. Effector recognition signals CKI release, which promotes RBR1 hyperphosphorylation, release of E2Fs, and transcription of pro-PCD genes. PCD results in cytoplasmic shrinkage and leakage of ions and DAMPs, and production of the immune signal salicylic acid to stimulate the immune response. In mammals, during pyroptosis, NLRs recognize intracellular pathogens through conserved MAMPs, triggering assembly of the inflammasome and activation of pyroptotic caspases. Pyroptotic death results in cell lysis and the release of DAMPs and inflammatory cytokines, leading to a full inflammatory response. DNA damage checkpoint-induced apoptosis includes an accumulation of hyperphosphorylated Rb as well as phosphorylation and stabilization of E2F1 by ATM and ATR, deregulating the Rb/E2F cell cycle pathway. The apoptosome is formed by interaction of procaspase 9 and cytochrome c, leading to activation of apoptotic caspases and a PCD phenotype that includes the formation of an apoptotic body.