Results demonstrate that Cu immunological impact is strongly time-dependent, and provide mechanistic support for incorporating recovery periods into CuSO4 treatment protocols to avoid unintended immunosuppression in aquaculture.
Abstract
Copper sulfate pentahydrate (CuSO4·5H2O) is widely used as a chemical prophylactic in aquaculture, yet its immunomodulatory effects in fish remain poorly understood. Here, we investigated how the timing of CuSO4 exposure shapes early immune responses and survival outcomes in channel catfish (Ictalurus punctatus) challenged with Flavobacterium covae. Channel catfish fingerlings were exposed to 2.1 mg/L CuSO4 either immediately before F. covae infection or following a 24 h recovery period, and gill transcriptomes were profiled at 1, 4, and 24 h post-challenge. Infection alone induced strong, time-structured innate and adaptive immune activation, including robust cytokine, chemokine, and pattern-recognition receptor (PRR) signaling. In contrast, Cu exposure followed by immediate infection produced no differentially expressed genes at 1 h and only a minimal response at 4 h, indicating a profound early suppression of host immune activation and a shift toward cellular stress-mitigation pathways. Fish that were treated with Cu followed by a 24 h recovery and then infected with F. covae regained immune responsiveness, displaying coordinated innate and adaptive activation by 4–24 h, consistent with significantly improved survival relative to immediate Cu exposure. Together, these results demonstrate that Cu immunological impact is strongly time-dependent. Acute exposure suppresses early immune readiness and increases susceptibility, whereas a recovery interval restores immune competence and enhances resistance to F. covae. These findings provide mechanistic support for incorporating recovery periods into CuSO4 treatment protocols to avoid unintended immunosuppression in aquaculture.
Photobacterium damselae subsp. piscicida (Pdp) is characterized by its broad distribution and is capable of infecting numerous cultured fish species. A previous study revealed the epidemic of Pdp in Lateolabrax maculatus with high mortality. In the current study, comparative transcriptome analysis was carried out on the spleens of L. maculatus infected with Pdp at 6, 12, and 24 hours post infection (hpi). The results demonstrated that compared with unchallenged individuals, Pdp infection resulted in 1631, 2085 and 2085 differentially expressed genes (DEGs) being detected at 6, 12 and 24 hpi, respectively. Among these, immune-related DEGs exhibited a trend of first increasing and then decreasing, particularly those involved in pattern recognition receptors, antigen processing and presentation, and inflammatory factors. In addition to terms related to immune system processes, GO enrichment analysis also identified terms related to signal transduction, metabolic processes, catalytic activity, and molecular function regulation. In KEGG enrichment analysis, numerous immune-related pathways were significantly enriched, such as the TNF signaling, NF-κB signaling, cytokine-cytokine receptor interaction, pattern recognition receptor, and natural killer cell mediated cytotoxicity. Subsequent weighted gene co-expression network analysis (WGCNA) uncovered immune-related pathways that were positively correlated at 6 and 12 hpi, and negatively correlated at 24 hpi, especially identified transcriptional trends suggesting Pdp may interfere with phagosome maturation and reduce endocytosis/autophagy-related gene expression at late infection stage. This study identified multiple immune-related genes and pathways that are dynamically regulated and potentially regulated by Pdp, which may contribute to its immune evasion and colonization in spotted sea bass. These findings provide new insights into the molecular immune mechanisms against Pdp infection and establish a basis for further studies on antibacterial defense in L. maculatus.
Jian Zhang, Dandan Zhou, Y. Gao et al.· Developmental and Comparativ...· 0 citations
Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.
Hongda Li, Tao Liu, Qiang Li et al.· Comparative Biochemistry and...· 0 citations
Molecular insights are offered into the molecular defense mechanisms of L. vannamei against A. pacificum toxicity as well as enriched pathways including lysosome, C‑type lectin receptor signaling, peroxisome, drug metabolism, and neuroactive ligand‑receptor interactions.
Fuyuan Zeng, Haiming Chen, Huijie Yang et al.· PLoS ONE· 0 citations
Dicyclohexyl phthalate (DCHP) is a widely used plasticizer, but its potential impact on immunity remains largely unexplored. In this study, synchronized L1-stage Caenorhabditis elegans were exposed to 0.0001–0.1 g/L DCHP for 72 h to investigate the effects of chronic early-life exposure on innate immunity; 0.01 and 0.1 g/L were used for subsequent mechanistic analyses. Innate immune function was evaluated using Pseudomonas aeruginosa PA14 survival assays, RT-qPCR, mutant strains, and oxidative-stress-related measurements. Chronic exposure beginning at the L1 stage significantly reduced the survival of C. elegans infected with Pseudomonas aeruginosa PA14. This immunosuppression was associated with increased daf-2 and age-1 transcript levels and reduced daf-16 transcript levels, indicating transcriptional alterations in insulin-like signaling-related genes. Additionally, the expression of pmk-1, nsy-1, and sek-1, key components of the p38 MAPK pathway, was markedly downregulated. Survival assays using different mutants supported the involvement of insulin-like signaling- and p38 MAPK-related genes in the decline in innate immunity following DCHP exposure. Furthermore, DCHP exposure reduced the expression of stress resistance genes, including skn-1, and several antioxidant enzymes. These findings suggest that DCHP may impair innate immune function through transcriptional alterations in immune- and stress-response pathways, although direct pathway activation or inhibition was not demonstrated.
Yuxuan Li, Siyuan Luo, Ming-Dian Lei et al.· Toxics· 0 citations
By damaging target tissues and compromising the host immune system, Myxobolus cerebralis and Tetracapsuloides bryosalmonae remain persistent threats to salmonids. RNA sequencing was used to assess transcriptome modulation in the kidney and head cartilage (HC) of rainbow trout during single and co-infections with these two myxozoan parasites. Fish were exposed to M. cerebralis (Mc) and T. bryosalmonae (Tb), and 30 days later, half of the fish from each group were subjected to sequential co-infections (Mc+ and Tb+). This assessment aimed to evaluate the combined effects of both pathogens. Transcriptomic analysis was conducted using kidney and HC tissues collected 60 days post-co-infection. The results showed that infection order altered host transcriptional profiles in a tissue-dependent manner. In the kidney, Tb fish showed pronounced transcriptional alterations linked to chronic inflammation, immune complex clearance, and IL-8-mediated responses. Tb+ fish exhibited broad immune activation in the kidney, suggesting dysregulated inflammatory responses likely associated with subsequent infection with M. cerebralis. In the kidney of Mc+ fish, the immune response was characterized by macrophage and IL signaling pathways. In HC, Mc fish activated Th17, IL-23, phagolysosome, and IL-6 cytokine pathways. In contrast, Mc+ fish showed increased pathogen processing and enhanced metabolic responses accompanied by suppression of cytokines and tissue repair processes. HC responses in Tb+ fish shifted toward IL-23, Th17-driven responses, alongside reduced developmental and extracellular matrix processes. The study establishes that host responses to myxozoan co-infection are shaped by tissue tropism and infection sequence, with distinct immune and tissue remodeling pathways activated in the target organs. These findings enhance the understanding of sequential T. bryosalmonae and M. cerebralis infections and provide a basis for identifying tissue-specific biomarkers and key immune targets. The findings may help identify methods for improved monitoring and management of myxozoan infections in salmonids.
Naveed Akram, Reinhard Ertl, R. Ghanei-Motlagh et al.· International Journal of Mol...· 0 citations