Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

Abstract

The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each meal is a potential infection because some bacteria have evolved mechanisms to resist predation. To survive such a hostile environment, D. discoideum has in turn evolved efficient antimicrobial responses that are intertwined with phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery and antimicrobial functions of these pathways are conserved in the mononuclear phagocytes of mammals, which mediate the initial, innate-immune response to infection. In this review, we discuss the advantages and relevance of D. discoideum as a model phagocyte to study cell-autonomous defenses. We cover the antimicrobial functions of phagocytosis and autophagy and describe the processes that create a microbicidal phagosome: acidification and delivery of lytic enzymes, generation of reactive oxygen species, and the regulation of Zn2+, Cu2+, and Fe2+ availability. High concentrations of metals poison microbes while metal sequestration inhibits their metabolic activity. We also describe microbial interference with these defenses and highlight observations made first in D. discoideum. Finally, we discuss galectins, TNF receptor-associated factors, tripartite motif-containing proteins, and signal transducers and activators of transcription, microbial restriction factors initially characterized in mammalian phagocytes that have either homologs or functional analogs in D. discoideum.

Calmodulin‐mediated events during the life cycle of the amoebozoan Dictyostelium discoideum

“…(Berchtold & Villalobo, ; Villalobo, ; Urrutia et al, ). The importance of D. discoideum as a model system to investigate fundamental biological processes and disease states is gaining increased attention (Annesley & Fisher, ; Huber, ; Dunn et al, ; Myre et al, ; Tatischeff, ). Here we show the critical role of CaM and its CaMBPs throughout the full developmental cycle of D. discoideum to emphasize its importance for continued study of specific cellular events and disease processes.…”

Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts byLegionella pneumophila

“…Within both D. discoideum and human macrophages, Rab5 and Rab7 act as the masterminds of governing phagosome maturation (Dunn et al, 2017; Gutierrez, 2013). Rab5 drives phagosome maturation by transporting V-ATPases from the trans-Golgi network (Gorvel, Chavrier, Zerial, & Gruenberg, 1991; C.…”

“…The foundation for the innate immune response came from cell-autonomous mechanisms in protists, which include lysozymes, ROS, metal poisoning, etc. (see (Dunn et al, 2017) for extensive review).…”

A brief historical and evolutionary perspective on the origin of cellular microbiology research

“…Following this line of research, D. discoideum has been used as a host cell model to study the cell‐intrinsic mechanisms active during infection by various animal and human pathogens such as Mycobacterium spp (Figure , bottom left panel), Legionella pneumophila , Salmonella enterica , Pseudomonas aeruginosa , Vibrio cholera , etc. (reviewed in Dunn et al, ).…”

“…Top panel: The Dictyostelium discoideum life cycle (Dunn et al, ). Bottom left panel: electron micrograph of an amoeboid cell of D. discoideum containing Mycobacterium marinum bacteria within a specialised phagosome (the mycobacteria‐containing vesicle); bottom right panel: a moving D. discoideum slug.…”