RESUMO
Infectious pancreatic necrosis virus (IPNV) primarily infects larvae and young salmonid with serious economic losses, which causes haemorrhage and putrescence of hepatopancreas. To develop a more effective oral vaccine against IPNV infection, the aeromonas hydrophila adhesion (AHA1) gene was used as a targeting molecule for intestinal epithelial cells. A genetically engineered Lactobacillus casei (pPG-612-AHA1-CK6-VP2/L. casei 393) was constructed to express the AHA1-CK6-VP2 fusion protein. The expression of interest protein was confirmed by western blotting and the immunogenicity of pPG-612-AHA1-CK6-VP2/L. casei 393 was evaluated. And the results showed that more pPG-612-AHA1-CK6-VP2/L. casei 393 were found in the intestinal mucosal surface of the immunized group. The Lactobacillus-derived AHA1-CK6-VP2 fusion protein could induce the production of serum IgM and skin mucus IgT specific for IPNV with neutralizing activity in rainbow trouts. The levels of IL-1ß, IL-8 and TNF-α isolated from the lymphocytes stimulated by AHA1-CK6-EGFP produced were significantly higher than EGFP group. For transcription levels of IL-1ß, IL-8, CK6, MHC-II, Mx and TNF-1α in the spleen, the result indicated that the adhesion and target chemokine recruit more immune cells to induce cellular immunity. The level of IPNV in the immunized group of pPG-612-AHA1-CK6-VP2/L. casei 393 was significantly lower than that in the control groups. These data indicated that the adhesion and target chemokine could enhance antigen delivery efficiency, which provides a valuable strategy for the development of IPNV recombination Lactobacillus casei oral vaccine in the future.
Assuntos
Infecções por Birnaviridae/veterinária , Doenças dos Peixes/prevenção & controle , Imunização/veterinária , Oncorhynchus mykiss/imunologia , Proteínas Estruturais Virais/imunologia , Vacinas Virais/administração & dosagem , Administração Oral , Animais , Anticorpos Antivirais/sangue , Infecções por Birnaviridae/prevenção & controle , Citocinas/imunologia , Doenças dos Peixes/virologia , Hepatopâncreas/patologia , Hepatopâncreas/virologia , Imunização/métodos , Imunização Secundária , Imunogenicidade da Vacina , Vírus da Necrose Pancreática Infecciosa , Lacticaseibacillus casei/genética , Oncorhynchus mykiss/virologia , Proteínas Estruturais Virais/administração & dosagem , Vacinas Virais/imunologiaRESUMO
Infectious pancreatic necrosis virus (IPNV) infects wild and cultured salmonid fish causing high mortality with serious economic losses to salmonid aquaculture. Ideally, the method of oral immunization should prevent the infection of rainbow trout juveniles with IPNV. In the present study, genetically engineered Lactobacillus casei 393 pPG-612-VP2/L. casei 393 and pPG-612-CK6-VP2/L. casei 393 constitutively expressing VP2 protein of IPNV were constructed. The recombinant strains pPG-612-CK6-VP2/L. casei 393 and pPG-612-VP2/L. casei 393 were orally administrated to juvenile rainbow trouts, and significant titers of IgM and IgT of pPG-612-CK6-VP2/L. casei 393 were observed. The results demonstrate that the recombinants could elicit both local mucosal and systemic immune responses. The proliferation of spleen lymphocytes in trouts immunized with pPG-612-CK6-VP2/L. casei 393 showed that the recombinant strain could induce a strong cellular immune response. The IL-1ß, IL-8, CK6, MHC-II, Mx, ß-defensin, and TNF-1α levels in the spleen and gut suggest that the target molecular chemokine has the ability to attract relevant immune cells to participate in the inflammatory response and enhance the function of the innate immune response. Additionally, the pPG-612-CK6-VP2/L. casei 393 induced the expression of cytokines, which have the effect of promoting inflammation to drive the differentiation of macrophages and clear target cells. After challenging with IPNV, the reduction in viral load caused by pPG-612-CK6-VP2/L. casei 393 was significantly higher than that of the other groups. Thus, the recombinant pPG-612-CK6-VP2/L. casei 393 is a promising candidate for the development of an oral vaccine against IPNV.
Assuntos
Infecções por Birnaviridae/prevenção & controle , Citocinas/imunologia , Doenças dos Peixes/prevenção & controle , Vírus da Necrose Pancreática Infecciosa , Lactobacillus/genética , Oncorhynchus mykiss/imunologia , Proteínas Estruturais Virais/imunologia , Administração Oral , Animais , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/veterinária , Linhagem Celular , Citocinas/genética , Doenças dos Peixes/imunologia , Imunização , Microrganismos Geneticamente Modificados , Proteínas Estruturais Virais/genéticaRESUMO
Viral infections frequently lead to the activation of host innate immune signaling pathways involved in the defense against invading pathogens. To ensure their survival, viruses have evolved sophisticated mechanisms to overcome the host immune responses. The present study demonstrated for the first time that infectious hematopoietic necrosis virus (IHNV) activated NF-κB pathway in fish cells. We further identified that the IHNV L protein could activate the NF-κB signaling pathway and that IHNV NV functioned as an inhibitor of NF-κB activation. Further results demonstrated that the NV protein blocked the degradation of the inhibitor of NF-κB (IκBα) and suppressed the SeV-induced NF-κB nuclear translocation. In conclusion, our study explored the functions of different IHNV proteins on NF-κB activation, and revealed a potential mechanism by which IHNV evades innate immune responses.
Assuntos
Doenças dos Peixes/genética , Proteínas de Peixes/genética , Vírus da Necrose Hematopoética Infecciosa/fisiologia , NF-kappa B/genética , Infecções por Rhabdoviridae/veterinária , Salmão , Proteínas Virais/metabolismo , Animais , Linhagem Celular , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Proteínas de Peixes/metabolismo , Imunidade Inata , NF-kappa B/metabolismo , Infecções por Rhabdoviridae/genética , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/virologia , Transdução de SinaisRESUMO
Background: Numerous observational studies have identified associations between both psoriasis (PsO) and psoriatic arthritis (PsA), and autoimmune diseases (AIDs); however, the causality of these associations remains undetermined. Methods: We conducted a bidirectional two-sample Mendelian Randomization study to identify causal associations and directions between both PsO and PsA and AIDs, such as systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), uveitis, bullous pemphigoid (BP), Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA), vitiligo, and ankylosing spondylitis (AS). The causal inferences were drawn by integrating results from four regression models: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, and Maximum Likelihood. Furthermore, we performed sensitivity analyses to confirm the reliability of our findings. Results: The results showed that CD [IVW odds ratio (ORIVW), 1.11; 95% confidence interval (CI), 1.06-1.17; P = 8.40E-06], vitiligo (ORIVW, 1.16; 95% CI, 1.05-1.28; P = 2.45E-03) were risk factors for PsO, while BP may reduce the incidence of PsO (ORIVW, 0.91; 95% CI, 0.87-0.96; P = 1.26E-04). CD (ORIVW, 1.07; 95% CI, 1.02-1.12; P = 0.01), HT (ORIVW, 1.23; 95% CI, 1.08-1.40; P = 1.43E-03), RA (ORIVW, 1.11; 95% CI, 1.02-1.21, P = 2.05E-02), AS (ORIVW, 2.18; 95% CI, 1.46-3.27; P = 1.55E-04), SLE (ORIVW, 1.04; 95% CI, 1.01-1.08; P = 1.07E-02) and vitiligo (ORIVW, 1.27; 95% CI, 1.14-1.42; P = 2.67E-05) were risk factors for PsA. Sensitivity analyses had validated the reliability of the results. Conclusions: Our study provides evidence for potential causal relationships between certain AIDs and both PsO and PsA. Specifically, CD and vitiligo may increase the risk of developing PsO, while CD, HT, SLE, RA, AS, and vitiligo may elevate the risk for PsA. Additionally, it is crucial to closely monitor the condition of PsO patients with specific AIDs, as they have a higher likelihood of developing PsA than those without AIDs. Moving forward, greater attention should be paid to PsA and further exploration of other PsO subtypes is warranted.
Assuntos
Artrite Psoriásica , Doenças Autoimunes , Análise da Randomização Mendeliana , Psoríase , Humanos , Artrite Psoriásica/genética , Doenças Autoimunes/genética , Doenças Autoimunes/epidemiologia , Psoríase/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Infectious hematopoietic necrosis virus (IHNV) infects salmonid fish, resulting in high mortality and serious economic losses to salmonid aquaculture. Therefore, an effective IHNV vaccine is urgently needed. To select an inactivation agent for the preparation of an effective IHNV vaccine, rainbow trout were immunized with mineral oil emulsions of IHNV vaccines inactivated by formaldehyde, binary ethylenimine (BEI), or ß-propiolactone (BPL). The fish were challenged 8 weeks after vaccination, and their IgM antibody response and relative percent survival (RPS) were evaluated. The results show that formaldehyde, BEI, and BPL abolished IHNV HLJ-09 infectivity within 24, 48, and 24 h at final concentrations of 0.2%, 0.02%, and 0.01%, respectively. The mean levels of specific IgM, both in serum and mucus (collected from the skin surface and gills), for the three immunized groups (from high to low) ranked as follows: the BPL group, BEI group, and formaldehyde group. From weeks 5 to 9, the mean log2 serum titers of IgM in the BPL group were significantly higher compared with those of the other groups (p < 0.05) during the 9 weeks of observation after vaccination (immunized at weeks 0 and6). Mucus OD490 values of the BPL group were significantly higher compared with those of the other groups (p < 0.05) when reaching their peak at weeks 5 and 8, but the difference between the formaldehyde and BEI groups was not significant (p > 0.05). The BPL-inactivated whole-virus vaccine had the greatest protective effect on the rainbow trout after challenge by an intraperitoneal injection of live IHNV, with an RPS rate of 91.67%, which was significantly higher compared with the BEI (83.33%) and formaldehyde (79.17%) groups. These results indicate that the BPL-inactivated IHNV oil-adjuvant vaccine was more effective than the formaldehyde- or BEI-inactivated vaccines. The results of this study provide an important foundation for further studies on inactivated IHNV vaccines.