FISH & SHELLFISH IMMUNOLOGY
·
2022
·
IF 4.622
Di Mu,Yu Jiang,Jing He,Yuanxing Zhang,Dahai Yang,Qin Liu,Zhuang Wang
Propolis is non-hazardous resinous substance mixture containing bioactive ingredients such as polyphenols, flavonoids and organic acid. It has been widely used as food supplement and immune adjuvant due to its benefits in anti-microbial and immunomodulation . Edwardsiella piscicida is a kind of threatening pathogen which could cause high mortality in turbot . However, whether propolis could enhance the innate immune response against E. piscicida infection in turbot remains unknown. In this study, we found dietary propolis addition could improve the expression of anti-oxidative stress related enzymes, e.g., SOD , CAT and GPT , and relieved the histopathological changes of juvenile turbot after E. piscicida infection. Moreover, propolis addition increased the expression of cytokines such as il-1β , il-6 and tnf-α in different organs of juvenile turbot. Importantly, rescued survival and decreased bacterial loads were observed in propolis feeding group. Taken together, these findings suggest that the important roles of propolis in protecting juvenile turbot from E. piscicida infection, indicating propolis might be applied as a promising immunopotentiator candidate in aquaculture.
研究领域:
水产养殖学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 13
·1906206
·
IF 11.459
Ting Tong,Hongwei Hu,Junwei Zhou,Shuangfei Deng,Xiaotong Zhang,Wantao Tang,Liurong Fang,Shaobo Xiao,Jiangong Liang
With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.
研究领域:
生物医学
·
病毒学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INVERTEBRATE PATHOLOGY
·
2025
·
IF 2.4
Yulian Peng,Jinliang Lyu,Qinwei Li,Petros Ligoxygakis,Yuxian Xia,Qi Xiao
The immune response of insects to pathogenic micro-organisms infection usually exhibits significant sex differences. Understanding this sexual dimorphism elucidates how immunity interplays with reproductive strategy, metabolic status and environmental factors. In this study, we showed female Drosophila melanogaster (fruit fly) survived better than males when infected with Metarhizium anisopliae CQMa421. This sex-specific survival difference depends on the Toll pathway, which is critical for innate immunity. We systematically compared innate immunity, including humoral immunity, cellular immunity, and melanization, between infected male and female flies. Female flies displayed a faster humoral immune response, characterized by earlier upregulation of antimicrobial peptides (AMPs) expression in both fat body and gut. On the other hand, male flies exhibited a stronger early cellular immune response, marked by increased expression of genes associated with hemocyte clotting and phagocytosis. While male flies upregulated melanization related Prophenoloxidase (PPO) earlier than female flies, both sexes significantly increased phenoloxidase (PO) activity after fungal infection. Fungal load quantification revealed that CQMa421 proliferated more quickly in females than in males. Collectively, our data indicate that each sex exhibits advantages in specific immune response, and that sex-biased survival outcome arises from the integration of multiple host defense mechanisms.
研究领域:
免疫学
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昆虫学
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分子生物学
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微生物与宿主互作
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产品关联
DOI
PubMed
高影响因子
Fish and Shellfish Immunology Reports
·
2021
·
IF 0
Jing He,Zhuang Wang,Yanbo Zhao,Jin Yang,Yuanxing Zhang,Qin Liu,Dahai Yang
Poly(I:C) is a kind of chemosynthetic double-stranded RNA (dsRNA) analogue which could act as TLR3 agonist and induce IFN production. It is widely applied in anti-virus treatment and immunoregulation, as well as vaccine adjuvant in farmed animals. However, whether poly(I:C) could activate innate immune response to defense against bacterial infection remains unclear. In this study, we established a feeding trial model with different dose of poly(I:C) in turbot larvae, then challenged with Edwardsiella piscicida after 3–7 weeks resting period. The results show that feeding turbot with poly(I:C) exhibited a stronger inflammatory response and antioxidant stress ability, and significantly elevated the survival rate within the decreased bacterial loads. Importantly, the bacterial infection-induced white feces in hindgut of turbot were significantly alleviated after poly(I:C) feeding, and this administration induced protection could last for about 7 weeks. Taken together, these findings indicate that feeding turbot with poly(I:C) could enhance a long-term intestinal mucosal immunity in response to bacterial infection, suggesting that poly(I:C) might be a promising immunostimulant in aquaculture.
研究领域:
水产养殖学
·
免疫学
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DOI
Nature Microbiology
·
2025
·
IF 19.4
Jin Shouheng,He Xing,Wang Zheyu,Zhou Tao,Wang Jun,Pan Guihong,Zhang Yin,Ma Ling,Yang Shuai,Wang Liqiu,Wu Yaoxing,Zou Yilin,Qi Nan,Cui Jun
Metabolic pathways determine cellular fate and function; however, the exact roles of metabolites in host defence against influenza virus remain undefined. Here we employed pharmacological inhibition and metabolomics analysis to show that the metabolic pathways of oxaloacetate (OAA) are integrated with antiviral responses to influenza virus. Cytosolic malate dehydrogenase 1 senses intracellular OAA to undergo dimerization and functions as a scaffold to recruit the transcription factor ETS2 for phosphorylation by the kinase TAOK1 at serine 313. The phosphorylated ETS2 translocates into the nucleus and supports optimal expression of TBK1, an indispensable activator of type I interferon responses. OAA supplementation provides a broad-spectrum antiviral ability, and OAA deficiency caused by Acly genetic ablation decreases antiviral immunity and renders mice more susceptible to lethal H1N1 virus infection. Our results uncover a signalling pathway through cellular OAA sensing that links metabolism and innate immunity to coordinate defence against viral challenge.
研究领域:
免疫学
·
病毒学
·
代谢生物学
·
分子生物学
·
信号转导
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感染与免疫
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产品关联
DOI
PubMed
高影响因子
NATURE IMMUNOLOGY
·
2020
·Vol. 21
·期 7
·727-735
·
IF 20.479
Jia Mutian,Qin Danhui,Zhao Chunyuan,Chai Li,Yu Zhongxia,Wang Wenwen,Tong Li,Lv Lin,Wang Yuanyuan,Rehwinkel Jan,Yu Jinming,Zhao Wei
Stimulator-of-interferon genes (STING) is vital for sensing cytosolic DNA and initiating innate immune responses against microbial infection and tumors. Redox homeostasis is the balance of oxidative and reducing reactions present in all living systems. Yet, how the intracellular redox state controls STING activation is unclear. Here, we show that cellular redox homeostasis maintained by glutathione peroxidase 4 (GPX4) is required for STING activation. GPX4 deficiency enhanced cellular lipid peroxidation and thus specifically inhibited the cGAS–STING pathway. Concordantly, GPX4 deficiency inhibited herpes simplex virus-1 (HSV-1)-induced innate antiviral immune responses and promoted HSV-1 replication in vivo. Mechanistically, GPX4 inactivation increased production of lipid peroxidation, which led to STING carbonylation at C88 and inhibited its trafficking from the endoplasmic reticulum (ER) to the Golgi complex. Thus, cellular stress–induced lipid peroxidation specifically attenuates the STING DNA-sensing pathway, suggesting that GPX4 facilitates STING activation by maintaining redox homeostasis of lipids.
研究领域:
免疫学
·
细胞生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2018
·
IF 2.913
Liangliang Mu,Xiaoxue Yin,Yanhui Xiao,Xia Bian,Yanjian Yang,Liting Wu,Jianmin Ye
Collectins, a subfamily of the C-type lectins, are able to bind non-self glycoconjugates on the surface of microorganisms and inhibit infection by direct neutralization, agglutination and/or opsonization , which play important roles in innate immunity . In this study, a CL11X1-like collectin (OnCL11X1) was identified from Nile tilapia ( Oreochromis niloticus ) and characterized at expression and agglutination functional levels. The open reading frame of OnCL11X1 is 840 bp of nucleotide sequence encoding polypeptides of 279 amino acids . The deduced amino acid sequence is highly homology to teleost and similar to mammalian CL11X1, containing a canonical collagen-like region, a carbohydrate recognition domain and a neck region. Expression analysis revealed that the OnCL11X1 was highly expressed in the liver, and widely exhibited in other tissues including kidney, intestines and spleen. In addition, the OnCL11X1 expression was significantly up-regulated in spleen and anterior kidney following challenges with a Gram-positive bacterial pathogen ( Streptococcus agalactiae ) and a Gram-negative bacterial pathogen ( Aeromonas hydrophila ). The up-regulation of OnCL11X1 expression was also demonstrated in hepatocytes and macrophages in vitro stimulation with S. agalactiae and A. hydrophila . Recombinant OnCL11X1 protein was able to agglutinate both S. agalactiae and A. hydrophila in vitro and promote the phagocytosis by macrophages. Taken together, the results of this study indicated that OnCL11X1, possessing apparent agglutination and opsonization ability to bacterial pathogens, might be involved in host defense against bacterial infection in Nile tilapia.
研究领域:
免疫学
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鱼类生物学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF THE WORLD AQUACULTURE SOCIETY
·
2024
·
IF 2.3
Lele Zhang,Fang Wang,Chunhui Lv,Lanliang Yu,Xiaojing Ci,Ning Zhang,Longwu Jia,Yuanyuan Xue,Xu Zhang,Xiaolei Su,Kai Wang
β-Catenin ( CTNNB ) is a core downstream mediator in the Wnt/β-catenin signaling pathway, which plays a role in immune regulation and cell differentiation. In the present study, two CTNNB genes were identified by genomic analysis of Hippocampus erectus and named He-CTNNB1 and He-CTNNB2 . He-CTNNB1 was more conserved than He-CTNNB2 . The full length of He-CTNNB1 was 2369 bp, including an open reading frame of 2275 bp that encoded 737 amino acids containing 12 armadillo repeats. Phylogenetic analysis revealed that He-CTNNB1 clusters had homologs in other bony fishes. Tissue distribution analysis showed the highest mRNA expression of He-CTNNB1 in the ovary, liver, and kidney of the lined seahorse under normal physiological conditions. The transcription level of He-CTNNB1 was significantly increased in the liver and kidney in response to LPS, poly I:C, and Edwardsiella tarda challenge ( p < 0.05). In vitro overexpression of He-CTNNB1 significantly upregulated the expression of key genes of the canonical Wnt/β-catenin signaling pathway, such as axin2 , cMyc , and cyclinD ( p < 0.05), which increased cell proliferation during the wound-healing process. Taken together, our results suggest that He-CTNNB1 is essential for cell proliferation and the innate immune response in H. erectus .
研究领域:
分子生物学
·
免疫学
·
鱼类生理学
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产品关联
DOI
高影响因子
Cell Reports
·
2025
·
IF 6.9
Li Chai,Chaoqun Li,Xuefeng Wang,Yanyang Qin,Hemin Sun,Jie Du,Liu Yang,Dongmei Hu,Jianan Xiong,Zhiyuan Zhao,Rong Gong,Tao Wu,Meng Wu,Meng Nie,Jialin Gao,Jihui Jia,Chengjiang Gao,Wei Zhao,Huan Zhou,Dongwei Kang,Mutian Jia
Perturbation of energy metabolism is an essential feature during infection and inflammation. TANK-binding kinase 1 (TBK1) is crucial for initiating the innate immune response against viral infection, although aberrant and ongoing TBK1 activation induces excessive production of type I interferons (IFN-I). Nonetheless, the mechanisms whereby energy metabolism controls TBK1 activation remain unclear. Here, we elucidate a mechanism linking energy metabolism to the inhibition of TBK1-induced IFN-I responses via the immune response gene 1 (IRG1)-itaconic acid axis. Mechanistically, itaconic acid and its derivatives alkylated TBK1 at Cys605, thereby disrupting TBK1 dimerization and rapid activation. IRG1, the enzyme that catalyzes itaconic acid production, is upregulated during late-phase viral infection and acts as a feedback regulator to restrain TBK1 activity. We developed itaconic acid-based compounds ITA-5/ITA-9 as alternative TBK1 inhibitors. ITA-5/ITA-9 effectively limited excess IFN-I-mediated hyperinflammation. These findings provide a promising therapeutic strategy for treating diseases mediated by aberrant TBK1 activation.
研究领域:
免疫学
·
分子生物学
·
代谢调控
·
先天免疫
·
病毒感染
·
信号转导
·
药物开发
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yan Fang,Feiyang Shen,Rui Huang,Yao Lin,Yijia Wu,Qian Li,Zhu Xie,Xiaoyu Yang,Zhe Zhang,Xiaoliang Jin,Xianqun Fan,Jianfeng Shen
The von Hippel–Lindau (VHL) tumor suppressor gene product, pVHL, is frequently deficient in a variety of human cancers. In addressing the treatment of pVHL-deficient tumors, hypoxia-inducible factor 2α (HIF-2α) has risen as a promising therapeutic target, culminating in the development of specific inhibitors like PT2385 and its analogues. Nonetheless, the absence of targeted delivery capabilities in these inhibitors heightens the risk of on-target toxicities. To mitigate these limitations, we have engineered a nanoparticle, termed PMMF (PT/MMSN@DSPE-PEG-FA), capable of delivering both a HIF-2α antagonist (PT2385) and manganese directly to tumor sites. PMMF has shown effective targeting of pVHL-deficient clear-cell renal cell carcinoma and melanoma, leading to significant therapeutic benefits and alleviating hypoxic and immunosuppressive traits of the tumor microenvironment. Functionally, PMMF boosts the cyclic GMP–AMP synthase–stimulator of interferon genes signaling pathway, which, in turn, stimulates a robust innate immune response. This response activates natural killer (NK) cells and CD8+ T lymphocytes while curbing the infiltration of regulatory T cells. Notably, the therapeutic efficacy of PMMF is markedly reduced when NK cells are blocked but not affected by neutrophil blockade, highlighting the critical role of NK cells in PMMF-induced antitumor immunity. Additionally, the safety profile of PMMF showed minimal systemic post-treatment cytotoxicity. In summary, our findings position PMMF as a promising platform for treating tumors with pVHL deficiency and underscore the therapeutic potential of metalloimmunotherapy.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
MICROBIOLOGICAL RESEARCH
·
2025
·
IF 6.9
Zheng Jia,Lingdi Niu,Junjie Guo,Jiaqing Wang,Hai Li,Runhang Liu,Ning Liu,Shuhe Zhang,Fang Wang,Junwei Ge
Regulation of the innate immune response may be an effective strategy to enhance Staphylococcus aureus vaccines. Based on our previous findings that the Listeria peptidoglycan skeleton (pBLP) enhances the immune response through an unknown mechanism, we hypothesized that pBLP provides protection by modulating the innate immune response via trained immunity. In vitro, pBLP increased phagocytosis and inflammatory cytokine levels and elevated the anti-inflammatory cytokine TGF-β following secondary stimulation. In an in vivo model, our findings indicate that pBLP, when administered with a vaccine, protects mice from methicillin-resistant S. aureus challenge and also provides protection against S. aureus CMCC26003 in the absence of antigens. Using an ex vivo model, we demonstrated that pBLP increases markers of trained immunity in peritoneal macrophages. Transcriptome analysis of differentially expressed genes and inhibitor experiments revealed that the trained immunity process induced by pBLP depends on mTOR-HIF-1α and hexokinase 2. This study is the first to demonstrate that pBLP can induce trained immunity. Furthermore, we show that the peptidoglycan skeleton induces a distinct trained immunity phenotype compared to β-glucan, enhancing vaccine protection. Our study provides valuable insights for the design of novel vaccines that integrate both specific and innate immune responses.
研究领域:
免疫学
·
微生物学
·
疫苗研发
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Honglei Zhang,Yizi Zhu,Jingxuan Ma,Yuqing Ma,Lijie Jin,Jing Li,Rui Yang,Gengshen Song
Lipid nanoparticle (LNP)-mRNA-based tumor immunotherapy needs to address challenges such as low efficacy of mRNA delivery, targeted protein expression, and compromised innate immunogenicity. Here, we screen a panel of 16 cyclic acetal-based ionizable lipid nanoparticles by in vitro and in vivo assays to develop a more effective and safer system specifically for tumor immunotherapy and mRNA delivery. Furthermore, by incorporating a cyclic acetal-based adjuvant lipid YK-TLR-001, two optimized cyclic acetal-based LNP formulations (YK-712 and YK-716) are demonstrated to enhance mRNA expression in the spleens and to induce exceptional maturation of antigen-presenting cells (APCs) and to promote antigen presentation. Moreover, animal studies treated with these formulations show activated cellular immunogenicity in healthy mice and inhibited tumor growth in the B16F10 melanoma model. Thus, the cyclic acetal-based LNPs with YK-TLR-001 present a promising direction in the design of mRNA vectors for the advancement of mRNA tumor immunotherapy.
研究领域:
生物医学工程
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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