Atlantic Salmon Pre-smolt Survivors of Renibacterium salmoninarum Infection Show Inhibited Cell-Mediated Adaptive Immune Response and a Higher Risk of Death During the Late Stage of Infection at Lower Water Temperatures

Abstract

Bacterial kidney disease (BKD) is widespread in many areas of the world and can cause substantial economic losses for the salmon aquaculture industry. The objective of this study was to investigate the pathophysiological response and gene expression profiles related to the immune response at different water temperatures and to identify the best immunopathological biomarkers to define a phenotype of resistance to BKD. The abundance of msa transcripts of R. salmoninarum in the head kidney was significantly higher in infected fish at 11 • C. R. salmoninarum induced significantly more severe kidney lesions, anemia and impaired renal function at 11 • C. In addition, the expression pattern of the genes related to humoral and cell-mediated immune responses in infected fish at 11 and 15 • C was very similar, although R. salmoninarum induced a significantly greater downregulation of the adaptive immune response genes at the lower water temperature. These results could be due to a suppressed host response directly related to the lowest water temperature and/or associated with a delayed host response related to the lowest water temperature. Although no significant differences in survival rate were observed, fish infected at the lowest temperature showed a higher probability of death and delayed the mortality curve during the late stage of infection (35 days after infection). Thirty-three immunopathological biomarkers were identified for potential use in the search for a resistance phenotype for BKD, and eight were genes related specifically to the adaptive cell-mediated immune response.

Lumpfish (Cyclopterus lumpus) Is Susceptible to Renibacterium salmoninarum Infection and Induces Cell-Mediated Immunity in the Chronic Stage

“…Further, Rozas-Serri et al. ( 106 ) demonstrated that the humoral and cell-mediated adaptive immune responses against R. salmoninarum in Atlantic salmon pre-smolts were significantly downregulated at the later stage of infection (55 dpi) ( 106 ), which agrees with our findings at 28 dpi. In contrast, most of the humoral-immune genes showed strong down-regulation at 28 dpi ( Figures 6A, C–E ), only the ighmc was significantly upregulated ( Figure 6F ).…”

“…This skewing towards the MHC-I pathway in lumpfish at the early stages of R. salmoninarum infection correlates with the BKD-dependent major histocompatibility-1 (mh1) induction observed in Atlantic salmon at 13 dpi (46). Further, Rozas-Serri et al (106) demonstrated that the humoral and cellmediated adaptive immune responses against R. salmoninarum in Atlantic salmon pre-smolts were significantly downregulated at the later stage of infection (55 dpi) (106), which agrees with our findings at 28 dpi. In contrast, most of the humoral-immune genes showed strong down-regulation at 28 dpi (Figures 6A, C-E), only the ighmc was significantly upregulated (Figure 6F).…”

“…In contrast, most of the humoral-immune genes showed strong down-regulation at 28 dpi ( Figures 6A, C–E ), only the ighmc was significantly upregulated ( Figure 6F ). This observation at 28 dpi is controversial but in line with the triggered humoral response against R. salmoninarum in salmonids, which does not necessarily correlate with immune protection ( 7 , 8 , 106 ).…”

Transcriptomic Profiling of the Adaptive and Innate Immune Responses of Atlantic Salmon to Renibacterium salmoninarum Infection

“…A genomics-based study used Suppression Subtractive Hybridisation (SSH) to identify BKD-responsive genes in Chinook salmon (15). A recent study reported expression responses of 22 genes (e.g., transcripts encoding interleukins and interferons) in the head kidney of Atlantic salmon infected with R. salmoninarum at different temperatures (16). Since vaccination with formalin-killed R. salmoninarum was found to enhance the resistance of salmonids to BKD (9), microarrays were previously used to profile the transcriptome response of Atlantic salmon to formalin-killed R. salmoninarum bacterin (17).…”

Temperature Variation and Host Immunity Regulate Viral Persistence in a Salmonid Host

“…The observation that colder temperatures (6 C) led to slower IHNV decay and higher mortality compared to warmer temperatures (10 and 15 C) may be a property associated with cold-water adapted pathogens. Clinical disease caused by several other salmon pathogens, including the bacteria Renibacterium salmoninarum and Flavobacterium pyschrophilum , are known to be exacerbated at colder temperatures [ 48 , 49 , 50 ]. Colder water is linked to high mortality and fish kills events of marine fish with VSHV [ 51 ].…”