JOURNAL OF INVERTEBRATE PATHOLOGY
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2025
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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
Small
·
2025
·
IF 12.1
Weitao Wang,Haitao Wu,Xuan Zhang,Yang Hong,Shi Tao,Xiangjing Cao,Shipeng Wang,Lisha Zha,Zhengbao Zha
Using entire tumor cells or tissues that display both common and patient-specific antigens can potentially trigger a comprehensive and long-lasting anti-tumor immune response. However, the limited immunogenicity, low uptake efficiency, and susceptibility to degradation of whole-component antigens present significant challenges. In this study, we employed tumor lysates (TLs) as whole-component antigens, in conjunction with MgAl-layered double hydroxide (MA) as nanoadjuvants and Mn 2+ as immunostimulants, to create personalized MMAT (Mn 2+ -MA-TLs) nanovaccines. After subcutaneous injection of MMAT nanovaccines, the high local concentrations of TLs and Mn 2+ facilitated the recruitment and activation of antigen-presenting cells (APCs), thereby inducing a robust adaptive immune response. Remarkably, MMAT nanovaccines enabled lysosomal escape, enhanced antigen cross-presentation, and activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in APCs. Furthermore, MMAT nanovaccines, when combined with the anti-TIGIT monoclonal antibody (aTIGIT), an immune checkpoint inhibitor, not only stimulated T-cell-based adaptive anti-tumor immune responses but also activated the NK-cell-based innate anti-tumor immunity, effectively suppressing tumor growth, recurrence, and metastasis. Thus, the ternary MMAT nanovaccines developed here introduced a pioneered paradigm for the rapid preparation of whole-component tumor antigens with nanoadjuvants and immunostimulants into nanovaccines, offering new prospects for clinical immunotherapies.
研究领域:
癌症免疫疗法
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免疫学
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纳米医学
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肿瘤生物学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2025
·
IF 3.9
Meiqin Mao,Zhixia Zhuang,Xiaoru Wang,Huabin Huang,Jiaonan Zhang,Jiaolin Zhang,Qingpi Yan
Pseudomonas plecoglossicida is a significant pathogen in aquaculture, capable of infecting various teleost fish and causing visceral white spot disease, which leads to substantial economic losses. The PhoP/PhoQ two-component system plays a central role in virulence regulation in Gram-negative bacteria; however, its specific function in P. plecoglossicida remains unclear. To elucidate the role of the phoP gene in the pathogenicity of this bacterium, we used hybrid grouper ( Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) as an infection model to compare the pathogenicity and host immune responses among the wild-type (NZBD9), phoP deletion (Δ phoP ), and complemented (C-Δ phoP ) strains. In artificial infection experiments, the Δ phoP strain exhibited significantly attenuated virulence, with an LD 50 value of 4.082 × 10 4 , which was 13.7 times higher than that of the wild-type strain. Furthermore, the deletion of phoP reduced bacterial load in the spleen and alleviated histopathological damage in the spleen, head kidney, and intestine. RNA-seq analysis of spleen tissue at 4 days post-infection identified 1768 differentially expressed genes (DEGs), including 704 up-regulated and 1064 down-regulated genes. GO and KEGG enrichment analyses revealed that these DEGs were primarily involved in immune-related processes and pathways, including TLR signaling, NF-κB activation, PI3K-Akt signaling, cytokine-cytokine receptor interaction, and cell adhesion molecules. Temporal expression profiling via qRT-PCR demonstrated that key immune genes (including tlr1, tlr5 , tlr13 , traf5 , nf-κb , mcp1 , cd3 , and il10 ) were generally down-regulated or exhibited delayed and weakened activation in Δ phoP -infected fish, indicating a subdued and dysregulated immune response. These results suggest that the phoP gene is essential for maintaining full virulence in P. plecoglossicida , modulating host immunity by suppressing critical inflammatory and immune signaling pathways. Our study provides novel insights into the role of the PhoP/PhoQ system in host–pathogen interactions and lays a theoretical foundation for developing targeted control strategies against P. plecoglossicida infection in aquaculture.
✓ 已验证
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2025
·
IF 2.7
Lisen Lin,Jiaqi Li,Chao Shang,Dapeng Li,Mingzhe Sun,Gaojie Song,Guangbo Qu,Xiao Li,Ran Zhu,Cuiling Zhang,Qinghao He,Guibin Jiang
Infectious bronchitis (IB) is an acute respiratory disease caused by the infectious bronchitis virus (IBV), spreads rapidly and manifests with diverse clinical signs, posing a major significant to the poultry industry. Metal ions such as copper are known to possess notable antiviral properties. Therefore, we evaluated the potential efficacy of copper-based pharmaceuticals against IBV. Results demonstrated that the copper-based drugs significantly protected DF-1 cells from IBV-M41 infection, markedly increasing cell activity and reducing IBV N-gene level. Furthermore, these drugs enhanced antiviral immunity and exhibited anti-apoptotic activity in vitro . In addition, these drugs increased the survival rates of infected chicken embryos and chicks while reducing developmental disruptions, thereby demonstrating robust antiviral effects. Pathological examinations revealed that lesions in the lungs, trachea, kidneys, spleen and other organs of treated groups improved to varying degrees, with a down-regulation of IBV N-gene level in chicks. Our study showed that the copper-based drugs exhibited anti-IBV-M41 both in vitro and in vivo , which provides a theoretical and experimental basis for exploring the anti-coronaviral effects of metal-based drug candidates.
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Zhixiang Cui,Hezhi Wang,Lu Qin,Ye Yuan,Jingwen Xue,Yalin An,Le Sun,Renfang Zhu,Qingyu Li,Yi Wang,Shuman Cui,Xuanguang Zhan,Qiyao Zhai,Haiyan Sun,Xin Zhang,Jian Guan,Chang Liu,Shirui Mao
The immunomodulatory effects and excellent tolerability of polysaccharides make them optimal candidates for pulmonary vaccine adjuvants. Yet, the structure–immunostimulatory activity relationship of polysaccharides remains unrevealed. Here, we developed nanovaccines decorated with four polysaccharides of distinct structures─hyaluronic acid (HA), pectin (PC), chondroitin sulfate (SC), and heparan sulfate (SH)─all sharing similar particle sizes and zeta potential. Polysaccharides containing sulfate groups (SC, SH) exhibited superior efficacy in overcoming natural inhalation barriers and recruiting dendritic cells (DC). DC stimulation assays revealed that HA and SH significantly upregulated the expression of costimulation signals, with IL-6 secretion rising over 8.7-fold compared to pure OVA. Fluorescence resonance energy transfer demonstrated their detachment within the lysosomal microenvironment, thereby enhancing antigen cross-presentation. However, in vivo findings only showed that SH upregulated CCR7 chemokine and swiftly migrated to lymph nodes. Molecular docking and Western blot analyses further elucidated the involvement of the TLR─MyD88─TRAF6─NF-κB/MAPK/IRF-7 signaling pathways. Notably, SH-modified nanovaccines induced a more robust cellular and humoral immune response with the potential for immune memory. This study confirms that sulfate groups in polysaccharides enhance immune activation and that combining sulfate with acetyl groups offers a promising adjuvant configuration for augmenting mucosal, cellular, and humoral immunity.
研究领域:
免疫学
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药剂学
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分子生物学
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Chuang Shen,Feng Huang,Yuxiang Wang,Yi Dai,Jianwei Chen,Yi Chen,Zhusheng Huang,Ying Zhang,Lixing Weng,Zhimin Luo,Yiqiao Hu,Lianhui Wang
Gynecologic malignancies are prone to metastasis and recurrence due to the low efficacy and sensitivity of current clinical treatments. Here, we construct ultrasmall Sb@Au nanodots (Sb@Au NDs) as a metallothionein 2A (MT 2A)-silencing nanoagonist for effective photothermal immunotherapy of gynecologic malignancies. Sb@Au NDs show high photothermal conversion efficiency of 56.8% under a 1270 nm laser and exceptional capability for downregulating MT 2A overexpressed in gynecologic malignancies. Synergizing mild photothermal therapy (PTT) with targeting downregulation of MT 2A based on Sb@Au NDs offers a robust therapeutic effect, significantly activating adaptive immune response and inhibiting the metastasis of gynecologic malignancies. RNA sequencing results of SKOV-3 cells elucidate that MT 2A downregulation by Sb@Au NDs impedes the transcription of zinc finger protein genes, thereby triggering the TGF-β signaling pathway, which blocks the cell cycle and activates the MAPK/c-fos apoptotic pathway to sensitize the treatment of gynecologic malignancies. Mild PTT synergizing with MT 2A downregulation by Sb@Au NDs can promote the secretion of β-defensin to increase the infiltration of CD4+ and CD8+ T cells and potentiate T-cell-mediated adaptive immune response. Our work provides an MT 2A-silencing nanoagonist for highly effective combination therapy and metastasis inhibition of gynecologic malignancies.
研究领域:
纳米医学
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癌症生物学
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免疫治疗
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分子生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
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2025
·
IF 5.5
Zhang Honglei,Ma Jingxuan,Jin Lijie,Ma Yuqing,Dong Kai,Li Jing,Yu Fei,Song Gengshen
Messenger RNA (mRNA) therapeutics have shown considerable promise across a wide range of medical applications with lipid nanoparticles (LNPs) emerging as the most clinically advanced mRNA delivery vehicles. However, the risk of off-target tissue delivery remains a concern, underscoring the need for diverse ionizable lipids to optimize LNP-based delivery systems. In this study, we designed and synthesized a library of 21 novel ionizable lipids and evaluated their potential for mRNA delivery. The resulting LNPs displayed favorable physicochemical properties and low cytotoxicity. In vitro transfection assay identified 3 high efficiency LNPs: YK-305, YK-310 and YK-319. In a mouse model, intramuscular injection of firefly luciferase (Fluc) mRNA-LNPs resulted in high transfection efficiency in muscle tissue, with significantly reduced gene expression in the liver. After encapsulating varicella zoster virus (VZV) glycoprotein E (gE)-encoding mRNA, the three LNP formulations induced robust humoral and cellular immune responses specific to the gE antigen, demonstrated improved selectivity and immunogenicity compared to SM-102, the ionizable lipid used in Moderna’s Spikevax. The safety of the gE-mRNA LNP formulations were subsequently demonstrated in a mouse model. Collectively, these findings provide a foundation for the optimization of tissue-targeting ionizable lipids and highlight their potential to advance mRNA-based vaccines in clinical applications. Graphical abstract
研究领域:
生物医学工程
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病毒学
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免疫学
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药学
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纳米技术
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DOI
PubMed
高影响因子
BIOMATERIALS
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2021
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IF 12.479
Si-Yuan Peng,Xin-Hua Liu,Qi-Wen Chen,Yun-Jian Yu,Miao-Deng Liu,Xian-Zheng Zhang
The overexpression of glutathione (GSH) in cancer cells has long been regarded as the primary obstacle for reactive oxygen species (ROS)-involved anti-tumor therapies. To solve this issue, a ferric ion and selenite-codoped calcium phosphate (Fe/Se–CaP) nanohybrid here is fabricated to catabolize endogenous GSH, instead of directly deleting it, to trigger a ROS storm for tumor suppression. The selenite component in Fe/Se–CaP can catabolize GSH to superoxide anion (O 2 •− ) and hydroxyl radicals (•OH) via cascade catalytic reactions , elevating oxidative stress while destroying antioxidant system. The doped Fe can further catalyze the soaring hydrogen peroxide (H 2 O 2 ) originated from O 2 •− to •OH via Fenton reactions. Collectively, Fe/Se–CaP mediated self-augmented catabolism dynamic therapy finally induces apoptosis of cancer cells owing to the significant rise of ROS and, combined with CaP adjuvant, evokes adaptive immune responses to suppress tumor progression, providing an innovative train of thought for ROS-involved anti-tumor therapies.
研究领域:
纳米技术
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癌症治疗
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生物化学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Chendong Yang,Yuanzhan Wang,Yuxue Han,Huiling Dong,Wei Tong,Xuanjun Wu
CpG oligodeoxynucleotides (ODNs) are synthetic Toll-like receptor 9 (TLR9) agonists that promote Th1-biased immune responses. However, their clinical utility is limited by rapid nuclease degradation and poor cellular uptake in antigen-presenting cells (APCs). To overcome this, we developed a pH-responsive nanoadjuvant, Ace-Dex-PC7A@CpG, composed of a cyclic seven-membered tertiary amine-based polymer (PC7A) grafted onto ethoxy-acetalated dextran (Ace-Dex) encapsulating CpG ODN 1668. In vitro, this nanoadjuvant significantly increased the levels of TNF-α, IL-6, IFN-β, and CXCL10 in RAW macrophages, indicating the simultaneous activation of both the TLR9 and stimulator of interferon genes (STING) pathways. In vivo, Ace-Dex-PC7A@CpG significantly enhanced the immunogenicity of the receptor-binding domain (RBD) of SARS-CoV-2, eliciting robust humoral responses with mean anti-RBD IgG titers exceeding 300,000, a 15-fold increase over free RBD (20,000). Sera from immunized mice showed >50% inhibition of RBD-hACE2 binding, far surpassing the 6% inhibition observed with free RBD. Furthermore, in a tumor-associated carbohydrate antigen (TACA) vaccine model, GM2-conjugated bacteriophage MX1 (GM2-MX1) virus-like particles (VLPs) adjuvanted with Ace-Dex-PC7A@CpG produced 10-fold higher anti-GM2 IgG titers than GM2-MX1 alone. More importantly, vaccination with 9NHAc-GD2-mQβ VLPs (a leading TACA vaccine candidate) plus Ace-Dex-PC7A@CpG significantly suppressed liver metastasis in an EL4 lymphoma model. These findings establish Ace-Dex-PC7A@CpG as a versatile nanoadjuvant for subunit vaccines against infectious diseases and cancer.
研究领域:
免疫学
·
纳米技术
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疫苗学
·
生物化学
·
分子生物学
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肿瘤学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhen Wang,Zhangyi Miao,Zhiting Cao,Jianye Ren,Xiaohong Zhu,Yu Sheng,Hao Cheng,Huaqing Zhang,Jianping Zhou,Yang Ding
Epicutaneous immunotherapy (EPIT) is effective and safe to induce sustained protection against anaphylaxis with small doses of allergens. To penetrate the barrier of the stratum corneum, a coaxial nanofiber patch is designed that incorporates natural phase-change materials (PCM) for mild hyperthermia-assisted skin permeability, while minimizing the risk of systemic events during immunotherapy. For adaptive immune activation, Toll-like receptor 7/8 ligand of resiquimod (R848) is combined with ovalbumin (OVA) allergen, thereby stimulating the Th1 pathway and strengthening therapeutic efficacy. For sequential administration, coaxial electrospinning technology is utilized for multiple drug encapsulation and sequential release, where the shell layer consists of poly(vinyl alcohol) (PVA) with OVA dispersion, and the core region is a mixture of PCM and R848. Under mild hyperthermia irritation, the nanofiber patches perform an efficient immunomodulation by manipulating the skin immune system via allergen/adjuvant combinations, which inhibits the secretion of OVA-specific IgE, and improves lung functions sufficiently in a mouse model of allergic asthma. Mechanistically, the treatment favors IgG2a expression from a Th1-biased immune response and induces protective regulatory immunity against allergen exposure. Overall, the simplicity and potency of mild hyperthermia mediated EPIT qualifies as a translational strategy for IgE-mediated allergies with long-lasting curative effects.
研究领域:
生物医学工程
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免疫治疗
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纳米技术
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药学
·
过敏与免疫学
✓ 已验证
产品关联
DOI
高影响因子
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