Immune Defences of Teleost Fish - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 17

includes the complement components which can either act directly on the pathogen or activate
membrane-bound PRRs, the complement receptors. Teleost fish produce an extensive array
of complement components which include C1q, C1r, C1s, C2, C3, C4, C5, membrane attack
complex (MAC) and complement receptors CR3, CR4 and C5aR. As such, complement
cascades and their receptors are involved in pathogen recognition, tagging, phagocytic clear-
ance, inflammation and chemotaxis, whereby other cells of the teleost immune system are
recruited to the site of pathogenic challenge (Boshra et al. 2006). The natural phagocytic cells
(macrophages and neutrophils) rely on recognition and phagocytosis of pathogenic material
via sugar/lectin interactions, CRP and also C3 binding to LPS in bacterial cell walls, and
MBL has been demonstrated to opsonize Aeromonas salmonicida in Atlantic salmon in the
absence of complement. The recognition and phagocytosis result in release of reactive oxygen
species (ROS) such as hydrogen peroxide, nitric oxide, peroxynitrite and hydroxyl radicals
as part of the respiratory burst (Secombes 1996; Lamas and Ellis 1994; Ottinger et al. 1999).
Indeed, this inducible NO response has been observed as a consequence of a faster and greatly
elevated expression of iNOS in the head kidney and gill tissue of rainbow trout Oncorhynchus
mykiss upon infection with Renibacterium salmoninarum (Campos-Perez et al. 2000).
In addition to soluble PRRs, membrane-bound PRRs are utilized by teleosts in the
phagocytic clearance of pathogens (non-signalling membrane-bound PRRs) and immune
inflammatory signalling resulting in cytokine expression and immune cell activation
(signalling membrane-bound PRRs). Signalling PRRs recognize a broad range of PAMPs
and are expressed according to location of pathogen, that is, they may be expressed on the
external surfaces of cell membranes responding to extracellular pathogens or may be located
on endosomal membranes in response to intracellular pathogens. Teleosts express TLRs 1, 2,
3, 4, 5, 5S, 7, 8, 9, 13, 14, 18, 19, 20, 21, 22 and 23 (reviewed in Jault et al. 2004; Rebl et al.
2010). The expression of TLRs 1, 2, 3, 4, 5, 7, 8 and 9 is conserved with humans; these PRRs
recognize and respond to lipopeptides, dsRNA, LPS, flagellin, ssRNA and CpG DNA, respec-
tively. Teleost fish express the additional receptors TLR14 (lipopeptides), TLR21 (CpG DNA),
TLR22 (dsRNA) and TLR23 (PAMP ligand unknown). Thus, in general, bacteria are recog-
nized by TLRs 1, 2, 4, 5, 9, 14 and 21 whereas viruses are recognized by TLRs 3, 7, 8, 9, 21
and 22. Of interest is the observation that TLR5 can exist as a soluble secreted form; whether
it acts as a signal enhancer or competitively inhibits flagellin binding to membrane TLR5 has
yet to be clarified. Teleost fish display evolutionary conserved expression of the signal adaptor
molecules Myd88, Mal, TRIF, TRAM and SARM and the downstream signal molecules
IRF3, IRF7 and NFκB (Purcell et al. 2006). Finally, the intracellular receptors NOD1 and
NOD2 are also conserved in teleost fish which is suggestive of innate responsiveness to
intracellular-resident bacterial pathogens. Of particular importance is the observation that
teleost fish also express endogenous negative regulators of TLR signalling such as DIGIRR
(Gu et al. 2011) and Tollip (Rebl et al. 2011); control by these is important to tolerance or the
switching off of innate responses to PAMP challenge. Thus, in the absence of these negative
regulators, dependent on which PRRs have been activated, the immune cell involved in recog-
nition of the PAMP can be activated and programmed towards either an anti-viral response
via IRF3- and IRF7-induced type I interferon production or an inflammatory response via
NFκB-dependent induction of pro-inflammatory cytokines such as TNFα and IL-1β.
The innate response is dependent on these cytokine signalling molecules produced by cells
such as the epithelial cells, macrophages, neutrophils and eosinophils. The cytokine profile
secreted determines amplitude and type of immune response to be raised against pathogens.