Disparate developmental patterns of immune responses to bacterial and viral infections in fish

Abstract

During early stages of development vertebrates rely on an immature immune system to fight pathogens, but in non mammalian species few studies have taken an in-depth analysis of the transition from reliance on innate immune mechanisms to the appearance of adaptive immunity. Using rainbow trout as a model we characterized responses to two natural pathogens of this species, the Gram negative bacterium Aeromonas salmonicida and the virus VHSV, using microarray analysis at four early life history stages; eyed egg, post hatch, first feeding and three weeks post first feeding when adaptive immunity starts to be effective. All stages responded to both infections, but the complexity of the response increased with developmental stage. The response to virus showed a clear interferon response only from first feeding. In contrast, bacterial infection induced a marked response from early stages, with modulation of inflammatory, antimicrobial peptide and complement genes across all developmental stages. Whilst the viral and bacterial responses were distinct, there were modulated genes in common, mainly of general inflammatory molecules. This work provides a first platform to explore the development of fish immunity to infection, and to compare the agedependent changes (from embryo to adults) across vertebrates.In most non mammalian vertebrates, pre-and post-hatch life occurs in an unpredictable, hostile external environment. This is in contrast to mammals where the embryo is in an almost sterile environment where pathogen exposure is controlled by the mother. Hence, fish eggs and embryos have to be able to fight efficiently against infections, and must possess active defence mechanisms.In teleost eggs, the first line of defence against invading pathogens is the physical barrier of the chorion and membranes 1,2 . Additionally, the embryonic membranes may express molecules to prevent bacterial and viral invasion, and may lack specific receptors for viral entry. The eggs at the early stages are also protected by maternally derived immune factors that are incorporated during vitellogenesis 3 , including complement components and other antimicrobial factors [4][5][6][7] . A number of critical transitions occur during embryo and fry development. Hatching is a first drastic change. Mouth and gut opening and first feeding stages represent another critical transition: as the gut microbiota is established 8 , interactions between the developing teleost immune system and the environment intensify, increasing dramatically the need for efficient defence mechanisms against pathogens. Importantly, lymphocytes and other components of adaptive immunity appear progressively and do not efficiently protect the fish until well after hatching.In fish as in other vertebrates, innate immunity is particularly important in early phases of development, when adaptive immunity is still not (fully) established and functioning. Triggering of innate receptors specific for pathogen-specific molecular patterns activates a variety of signalling pathways. Generi...

Growth hormone transgenesis disrupts immune function in muscle of coho salmon (Oncorhynchus kisutch) impacting cross-talk with growth systems

“…To assess skeletal muscle responses to PGN, we measured transcript levels for markers of pro-inflammatory cytokines (TNFα, IL-1β, and IL-8) and acute phase proteins (SAA and HAMP) (Fig. 2A; Table S2) after Castro et al 2015. A response to PGN was detected in each group, evidenced by a significant induction of all tested marker genes barring TNFα in TF (Fig.…”

“…To assess skeletal muscle responses to Poly:IC, we measured transcript levels for markers of cytokines and proteins involved in the antiviral response (IFN-a, y-IP, Mx, LMP2 and RSAD2) (Fig. 2B; Table S2) after Castro et al 2015. Each tested marker was significantly induced in WT and TR, but not TF (Fig.…”

“…A past study identified salmonid-specific duplicates of GHR (GHR1 and GHR2), including in coho salmon (Very et al 2005), for which we designed new primer pairs that bind divergent regions among the duplicates (Table S1). Additional primers were used for marker genes known to be strongly upregulated by immune stimulation or to be directly involved in muscle growth and development (described in: Castro et al 2015; Alzaid et al, 2016a, 2016b).…”

Next-generation salmonid alphavirus vaccine development

“…The age of the fish has been shown to play a role in vaccine efficacy, because while innate immunity is effective immediately after hatching, adaptive immunity needs time to mature (Castro et al, 2015). Rainbow trout and Atlantic salmon have been shown to be fully immunocompetent at 2-3 months and 5 grams of age, respectively (Lillehaug, 2014).…”