Evidence of Trained Immunity in a Fish: Conserved Features in Carp Macrophages

Abstract

Trained immunity is a form of innate immune memory best described in mice and humans. Clear evidence of the evolutionary conservation of trained immunity in teleost fish is lacking. Given the evolutionary position of teleosts as early vertebrates with a fully developed immune system, we hypothesize that teleost myeloid cells show features of trained immunity common to those observed in mammalian macrophages. These would at least include the ability of fish macrophages to mount heightened responses to a secondary stimulus in a nonspecific manner. We established an in vitro model to study trained immunity in fish by adapting a well-described culture system of head kidney-derived macrophages of common carp. A soluble NOD-specific ligand and a soluble b-glucan were used to train carp macrophages, after which cells were rested for 6 d prior to exposure to a secondary stimulus. Unstimulated trained macrophages displayed evidence of metabolic reprogramming as well as heightened phagocytosis and increased expression of the inflammatory cytokines il6 and tnf-a. Stimulated trained macrophages showed heightened production of reactive oxygen and nitrogen species as compared with the corresponding stimulated but untrained cells. We discuss the value of our findings for future studies on trained immunity in teleost fish.

Intestinal Explant Cultures from Gilthead Seabream (Sparus aurata, L.) Allowed the Determination of Mucosal Sensitivity to Bacterial Pathogens and the Impact of a Plant Protein Diet

“…Increased expression of IL-1β and COX-2 has been reported before after in vitro challenge of gilthead seabream immune cells with bacteria or commercial pathogen-associated molecular pattern (PAMP) solutions [ 47 , 48 , 49 , 50 ]. Although COX-2 is a typical oxidative stress marker, its expression is also induced by inflammatory mediators [ 49 , 51 ], including IL-1β [ 52 ], as it takes part in the production of reactive oxygen species (ROS) and NO that have antibacterial activity and are also part of the innate immune system in higher vertebrates and carp macrophages [ 53 , 54 ]. In addition, genes related to the maintenance of epithelial tissue integrity, such as Ocl (expressing occludin), are influenced by inflammatory processes [ 55 , 56 ], and its regulation depends on several cytoskeletal, scaffolding, signaling, and polarity proteins [ 42 ], and it is definitely related to epithelial barrier functions in vivo and in vitro [ 56 ].…”

Intestinal Explant Cultures from Gilthead Seabream (Sparus Aurata, L.) Allowed Determining the Mucosal Sensitivity to Bacterial Pathogens and the Impact of a Plant Protein Diet

“…Increased expression of IL-1β and COX-2 has been reported before after in vitro challenge of gilthead seabream immune cells with bacteria or commercial pathogen associated molecular pattern (PAMP) solutions [56][57][58][59]. Although COX-2 is a typical oxidative stress marker, its expression is also induced by in ammatory mediators [58,60], including IL-1β [61], as it takes part in the production of reactive oxygen species (ROS) and NO that have antibacterial activity and are also part of the innate immune system in higher vertebrates and carp macrophages [62,63]. Also genes related to the maintenance of the epithelial tissue integrity, such as Ocl (expressing occludin), are in uenced by in ammatory processes [64,65], and its regulation depends on several cytoskeletal, scaffolding, signalling and polarity proteins [51] and it is de nitely related to epithelial barrier functions in vivo and in vitro [65].…”

Could the Induction of Trained Immunity by β-Glucan Serve as a Defense Against COVID-19?

“…A study conducted by Medina-Gall et al that used zebrafish intraperitoneally injected with β-glucan and then subsequently challenged with spring viremia of carp virus (SVCV), a deadly virus that causes significant mortality in carp populations, supported this. Here they showed that β-glucan treated fish exhibited a significant increase in survival at 14 days post-treatment ( 23 , 38 , 39 ).…”