Non-adjuvanted flagellin elicits a non-specific protective immune response in rainbow trout (Oncorhynchus mykiss, Walbaum) towards bacterial infections

Re-examination of the rainbow trout (Oncorhynchus mykiss) immune response to flagellin: Yersinia ruckeri flagellin is a potent activator of acute phase proteins, anti-microbial peptides and pro-inflammatory cytokines in vitro

“…TNF-α can be expressed by multiple cell types, including macrophages, Th1 cells, Th2 cells and Th17 cells and acts to potentiate the ongoing immune response by increasing the transcription of critical Th1 or Th2 cytokines . The ability of flagellin to induce the expression of pro-inflammatory cytokines, and in synergy with a type 1 cytokine (IFN-γ) to up-regulate the expression of specific isoforms of IL-12 and TNF-α isoforms, suggests that flagellin has the potential to be an immune stimulant or adjuvant in future novel vaccines for fish aquaculture as suggested by others (Hynes et al, 2011;Scott et al, 2013;Gonzalez-Stegmaier et al, 2015).…”

“…With the recent success in characterising many salmonid cytokine genes, most of which have multiple paralogues, it was clear that the effects of flagellin on the fish immune system needed to be revisited. Moreover, a flagellin from the pathogenic bacterium Y. ruckeri has been shown to induce a non-specific protection against a variety of bacterial pathogens in vivo in rainbow trout (Scott et al, 2013) but the mechanism(s) of this flagellin-mediated protection is unknown. The results from the present study go some way to address these issues.…”

“…The induction of APPs and AMPs by rYRF is particularly interesting in the context of the nonspecific protection seen after flagellin administration in vivo (Scott et al, 2013). Clearly these molecules may contribute to induction of an antimicrobial state.…”

“…Both the TLR5M and TLR5S recognize flagellin from the Gram negative bacterium Vibrio anguillarum. The immune responses to flagellin have been examined in salmonids and other fish species recently (Chettri et al, 2011;Hynes et al, 2011;Scott et al, 2013;Gonzalez-Stegmaier et al, 2015), where up-regulation of IL-1β and IL-8 expression is seen to flagellins from V. anguillarum and B. subtilis. Curiously the response was one order of magnitude lower in rainbow trout than in gilthead seabream (Sparus aurata) (Gonzalez-Stegmaier et al, 2015), although this may be related to speciesorigin of the flagellin.…”

“…Indeed, the recent identification of multiple paralogues of many cytokines in fish (eg in salmonids there are three each of IL-1β and TNFα) (Husain et al, 2012;Hong et al, 2013) means the cytokine response to flagellin stimulation is far from complete. Moreover, a flagellin from the pathogenic bacterium Yersinia ruckeri, the causative agent of enteric redmouth disease (ERM) that primarily affects farmed salmonids (Harun et al, 2011), has been shown to induce non-specific protection against a variety of bacterial pathogens in vivo in rainbow trout (Scott et al, 2013). However, the mechanism(s) of flagellin-mediated nonspecific protection in fish is largely unknown.…”