The gnotobiotic brine shrimp (Artemia franciscana) model system reveals that the phenolic compound pyrogallol protects against infection through its prooxidant activity

The phenolic compound pyrogallol is the functional unit of many polyphenols and currently there has been a growing interest in using this compound in human and animal health owing to its health-promoting effects. The biological actions of pyrogallol moiety (and polyphenols) in inducing health benefitting effects have been studied; however, the mechanisms of action remain unclear yet. Here, we aimed at unravelling the underlying mechanism of action behind the protective effects of pyrogallol against bacterial infection by using the gnotobiotically-cultured brine shrimp Artemia franciscana and pathogenic bacteria Vibrio harveyi as host-pathogen model system. The gnotobiotic test system represents an exceptional system for carrying out such studies because it eliminates any possible interference of microbial communities (naturally present in the experimental system) in mechanistic studies and furthermore facilitates the interpretation of the results in terms of a cause effect relationship. We provided clear evidences suggesting that pyrogallol pretreament, at an optimum concentration, induced protective effects in the brine shrimp against V. harveyi infection. By pretreating brine shrimp with pyrogallol in the presence or absence of an antioxidant enzyme mixture (catalase and superoxide dismutase), we showed that the Vibrio-protective effect of the compound was caused by its prooxidant action (e.g. generation of hydrogen peroxide, H₂O₂). We showed further that generation of prooxidant is linked to the induction of heat shock protein Hsp70, which is involved in eliciting the prophenoloxidase and transglutaminase immune responses. The ability of pyrogallol to induce protective immunity makes it a potential natural protective agent that might be a potential preventive modality for different host-pathogen systems.