All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previously, we described a Caenorhabditis elegans-Pseudomonas aeruginosa assay (Liquid Killing) in which toxicity to the host is dependent upon the secreted bacterial siderophore pyoverdine. Although pyoverdine is also indispensable for virulence in mammals, its cytological effects are unclear. We used genetics, transcriptomics, and a variety of pathogen and chemical exposure assays to study the interactions between P . aeruginosa and C . elegans . Although P . aeruginosa can kill C . elegans through at least 5 different mechanisms, the defense responses activated by Liquid Killing are specific and selective and have little in common with innate defense mechanisms against intestinal colonization. Intriguingly, the defense response utilizes the phylogenetically-conserved ESRE (Ethanol and Stress Response Element) network, which we and others have previously shown to mitigate damage from a variety of abiotic stresses. This is the first report of this networks involvement in innate immunity, and indicates that host innate immune responses overlap with responses to abiotic stresses. The upregulation of the ESRE network in C . elegans is mediated in part by a family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions. Our data convincingly show that, following exposure to P . aeruginosa , the ESRE defense network is activated by mitochondrial damage, and that mitochondrial damage also leads to ESRE activation in mammals. This establishes a role for ESRE in a phylogenetically-conserved mitochondrial surveillance system important for stress response and innate immunity. Author summary It is increasingly clear that living organisms surveil their cellular structures and physiology to gain early warning about the presence and activity of pathogens or abiotic threats (like hypoxia, hyper- or hypothermia, oxidative damage, etc.). Upon recognizing dysfunction, host defense networks are engaged to prevent and mitigate the damage. Here we report the involvement of a phylogenetically-conserved defense network, called ESRE, in mitochondrial surveillance in C . elegans and mammals. Our report expands the function of this network to include innate immunity in addition to its role in abiotic stress response. We also observed that a variety of mitochondrial poisons, and the opportunistic human pathogen Pseudomonas aeruginosa , activate the ESRE network, suggesting that mitochondrial surveillance is a key facet of its regulation. Since mitochondrial health is an important factor in many diseases, having a better understanding of how cells perceive and respond to damage to this organelle is critical for understanding numerous aspects of human health.
【초록키워드】 Diseases, innate immune response, Stress, hypoxia, Innate immunity, threat, transcriptomics, Infection, Toxicity, genetics, Ethanol, Protein, family, Health, pathogen, Surveillance, immune responses, response, Physiology, Pathogens, stress response, mechanisms, oxidative damage, virulence, Critical, mechanism, homeostasis, Bacterial, Interaction, Pseudomonas aeruginosa, host defense, defense mechanisms, leads, Caenorhabditis elegans, mitochondrial, exposure to, dysfunction, overlapping, Imbalance, hypothermia, Activation, Organisms, Regulation, overlap, battery, damage, upregulation, human pathogen, organism, functions, organelle, liquid, mammals, selective, heat, Defense, element, elegans, pyoverdine, Host, Effect, mitigate, Prevent, Cell, intestinal, cytological, shown, described, include, addition, activated, indicate, unique, variety, recognizing, activate, respond, expand, increasingly, Caenorhabditis, elegan, kill, cellular structure, P . aeruginosa, secreted, 【제목키워드】 Surveillance, pathway, mitochondrial, Defense, conserved, required,