Innate immunity depends on the recognition of pathogens and subsequent regulation of complex interactions that ultimately leads to production of compounds to deter microbial innovation. This thesis presents different aspects of immunity-associated cell death with focus on autophagy in the plant Arabidopsis and human cells.
ACCELERATED-CELL-DEATH11 (ACD11) is an Arabidopsis mutant that shows spontaneous and lethal cell death dependent on activation of the resistance protein LAZ5, a cytoplasmic receptor of the TIR-NB-LRR type. In a screen for suppressors of acd11-associated cell death, laz4, a component of the retromer complex, was discovered as a relatively weak suppressor. Here I show redundancy between the three VPS35 homologs present in Arabidopsis in regulation of immunity-associated cell death, with a focus on the catabolic pathway autophagy. In addition a role for ACD11 in sphingolipid metabolism and its role in plant innate immunity will be presented.
A homolog of ACD11 in humans is FOUR-PHOSPHATE ADAPTOR PROTEIN2 (FAPP2) and it has also been shown to be involved in cell death regulation in human Jurkat T cells. The data presented here show that FAPP2 does not appear to be involved in cell death regulation in human HeLa cells, contrasting previous observations.
Autophagy is a catabolic pathway involved in both pro-life and pro-death regulation of stress and cell death. The pathway has previously been shown to be controlled through NPR1, a central regulator for the phyto-hormone salicylic acid. Here, I present data that make it clear that NPR1 does not directly regulate autophagy, but instead control stress responses that indirectly activate autophagy. The observations presented will also clarify why autophagy has been described as being both a pro-death and pro-life pathway under similar conditions.