Endotoxin recognition: In fish or not in fish?

Abstract

The interaction between pathogens and their multicellular hosts is initiated by activation of pathogen recognition receptors (PRRs). These receptors, that include most notably members of the toll-like receptor (TLR) family, recognize specific pathogen-associated molecular patterns (PAMPs). TLR4 is a central part of the receptor complex that is involved in the activation of the immune system by lipopolysaccharide (LPS) through the specific recognition of its endotoxic moiety (Lipid A). This is a critical event that is essential for the immune response to Gram-negative bacteria as well as the etiology of endotoxic shock. Interestingly, compared to mammals, fish are resistant to endotoxic shock. This in vivo resistance concurs with in vitro studies demonstrating significantly lowered sensitivity of fish leukocytes to LPS activation. Further, our in vitro analyses demonstrate that in trout mononuclear phagocytes, LPS fails to induce antiviral genes, an event that occurs downstream of TLR4 and is required for the development of endotoxic shock. Finally, an in silico approach that includes mining of different piscine genomic and EST databases, reveals the presence in fish of all of the major TLR signaling elements except for the molecules specifically involved in TLR4-mediated endotoxin recognition and signaling in mammals. Collectively, our analysis questions the existence of TLR4-mediated cellular responses to LPS in fish. We further speculate that other receptors, in particular beta-2 integrins, may play a primary role in the activation of piscine leukocytes by LPS.

CpG- and LPS-activated MAPK signaling in in vitro cultured salmon (Salmo salar) mononuclear phagocytes

“…It has been shown that in vitro cultured trout HK-derived adherent monocytes differentiate spontaneously and following incubation for several days develop a more mature, macrophage-like phenotype. This is manifested by changes in their morphology and enhanced potential to respond to LPS stimulation [17,28,29]. In the current study, the non-stimulated salmon primary cells displayed similar morphological changes when cultured in vitro for a period of 3 to 5 days (Fig.…”

Mechanisms of intrinsic resistance to antimicrobial peptides of Edwardsiella ictaluri and its influence on fish gut inflammation and virulence

“…Fish have no or a poor inflammatory immune response to LPS (Berczi et al, 1966;Iliev et al, 2005;Swain et al, 2008). However, there are, to our knowledge, no studies about fish intestinal gut inflammation related to Edwardsiella LPS.…”

“…6h, i). Several reports suggest that fish do not respond to LPS mainly because of the lack of PLB, CD14 and TIRF1, essential components for the function of Toll-like receptor 4 (Iliev et al, 2005). Adult fish or zebrafish i.c.…”

Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates

“…Homologs of TI-CAM2 have not been identified in teleosts [15,16,40], Xenopus, [22] or chickens [17,23], except in mammals and sharks [21]. As two TICAM homologs were identified in lamprey [14], Iliev et al [40] assumed that a TI-CAM2 ortholog existed in the common predecessor of fish and tetrapods. Sullivan et al confirmed this hypothesis and went further by suggesting that TICAM2 was probably lost after the divergence of rayfin and lobefin fishes 450 million years ago [17].…”

“…In the early vertebrates, TICAM1 is evolutionarily conserved and easily identified [40]. Homologs of TI-CAM2 have not been identified in teleosts [15,16,40], Xenopus, [22] or chickens [17,23], except in mammals and sharks [21].…”