Regulated cell death in fungi from a comparative immunology perspective

The death of fungal cells has been studied in a variety of contexts including responses to antifungal drugs, during fungal developmental processes, in response to bacterial or mycoviral fungal pathogens, and during non-self-recognition between distinct strains of the same species (allorecognition). Some of the genetic determinants and molecular mechanisms of fungal cell death processes are now beginning to be understood in detail. Recent advances have uncovered fungal cell death machinery that shares ancestry with key actors of immune cell death in other eukaryotic and prokaryotic taxa. Transkingdom evolutionary links include fungal molecular sensors such as NOD-like receptors and signaling domains related to the TIR (Toll/interleukin-1 receptor) family, which are a staple of immunity throughout the tree of life. Moreover, cell death executioner proteins homologous to the pore-forming proteins that mediate mammalian necroptosis and pyroptosis are also abundant and widespread in fungi, particularly in Ascomycota. These findings prompt us to speculate on the possible origins of fungal cell death and to reconsider fungal innate immunity beyond allorecognition. This review discusses historical landmarks and major recent discoveries regarding the regulation of cell death processes in fungi through the lens of immunity.