Innate immunity in fungi: Is regulated cell death involved?

Innate immunity is an ancient cell-autonomous property of eukaryotes that allows them to regulate interactions with antagonistic microbes, including bacteria. While animal and plant innate immunity systems are relatively well understood [1,2], innate defenses in fungi are only beginning to be unraveled. Both animal and plant immune systems consist of surveillance, signal transduction, and response modules, which exhibit remarkable functional similarities and are clearly products of convergent/parallel evolutionary trajectories [3,4]. Among others, these similarities include regulated cell death (RCD) of infected cells as an ultimate mechanism for eliminating microbial intruders. Unlike accidental cell death, RCD is governed by a set of genetically encoded procedures for targeted cell removal and, depending on specific stimuli, can proceed along several distinct pathways manifested by diverse biochemical and morphological hallmarks [5]. It is unclear whether the convergent patterns in animal and plant innate defenses are a consequence of (i) adaptation to similar selective forces exerted by microbial antagonists; (ii) underlying physical, biochemical, or developmental constraints imposed by solutions needed to combat invading microbes; (iii) stochasticity of genetic drift; or (iv) a combination of all these 3 forces [6]. Nonetheless, it is not unreasonable to expect that elements of innate immunity have also evolved in fungi. The limited knowledge about antimicrobial defenses in fungi could be attributed to the common perception that fungi depend on secondary metabolites to suppress bacterial antagonists [7]. Indeed, secondary metabolites, which are nonessential bioactive compounds of low molecular weight, play an outsized role in warfare and defense of some fungi, particularly Dikarya [8]. However, other fungi, including those representing early divergent lineages, such as Mucoromycotina, do not produce extensive repertoires of secondary metabolites and seem to rely on mechanisms resembling innate immunity of animals and plants for protection of their cells from bacterial invasions [9], as we detail in the subsequent sections. Given convergent origins of animal and plant antimicrobial defenses, the existence of innate immunity in fungi is not surprising. Its architecture is likely a product of both, a close phylogenetic relation of fungi and animals, which are united in the supergroup Opistokonta, and physical constrains of a modular growth habit and rigid walls enveloping fungal cells, both features shared with plants. Because of these conditions, fungi are expected to share molecular underpinnings of their immune responses with animals, while being able to mount them in most vegetative cells of their bodies, like plants and in contrast to animals, which rely on specialized immune cells, phagocytes. In this Pearl, we outline the convergently evolved innate immune modules of animals and plants, argue that antibacterial defenses of fungi exhibit hallmarks of innate immunity, explore the types of RCD in fungi, hypothesize that RCD is one of the defensive responses in fungi, PLOS PATHOGENS