INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yangxi Xiang,Yue Shi,Lianlian Sun,Weikang Liang,Kaiyu Chen,Chenghua Li
Pattern recognition receptors (PRRs) mediate the innate immune responses and play a crucial role in host defense against pathogen infections. Apextrin C-terminal (ApeC)-containing proteins (ACPs), a newly discovered class of PRRs specific to invertebrates, recognize pathogens through their ApeC domain as intracellular or extracellular effectors. However, the other immunological functions of ACPs remain unclear. In this study, a membrane-localized ACP receptor was identified in the sea cucumber Apostichopus japonicus (denoted as AjACP1). The ApeC domain of AjACP1, which was located outside of its cell membrane, exhibited the capability to recognize and aggregate Vibrio splendidus . AjACP1 was upregulated upon V. splendidus infection, internalizing into the cytoplasm of coelomocytes. AjACP1 overexpression enhanced the phagocytic activity of coelomocytes against V. splendidus , while knockdown of AjACP1 by RNA interfere inhibited coelomocyte endocytosis. Inhibitor experiments indicated that AjACP1 regulated coelomocyte phagocytosis through the actin-dependent endocytic signaling pathway. Further investigation revealed that AjACP1 interacted with the subunit of the actin-related protein 2/3 complex ARPC2, promoting F-actin polymerization and cytoskeletal rearrangement and thereby affecting the coelomocyte phagocytosis of V. splendidus via the actin-dependent endocytic signaling pathway. As a novel membrane PRR, AjACP1 mediates the recognition and phagocytic activity of coelomocytes against V. splendidus through the AjACP1-ARPC2-F-actin polymerization and cytoskeletal rearrangement pathway.
研究领域:
免疫学
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海洋生物学
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分子生物学
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2023
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IF 19
Jun-Jun Wu,Guan-Jie Chen,Chen-Yuan Fan,Fan Shen,Yi Yang,Wei Pang,Zhen-Nan Zhao,Hong-Xin Guan,Huan Wu,Ying Lu,Ya-Juan Fu,Qi Chen,Yong-Tang Zheng,Songying Ouyang
The pandemics induced by emerging SARS-CoV-2 variants and monkeypox virus infection have triggered the urgent need for broad-spectrum vaccines. Except for “super” antigen designs, pattern recognition receptor (PRR) agonist-based adjuvants might blaze a new trail, through enhancing the immune response of conserved antigen epitopes shared among variants for cross-protection. Ideal adjuvants with proper adjustments could be conveniently applied to different antigens and antigen types in response to new pandemics. However, general strategies for modulating PRR agonist-based adjuvant properties to tailor the optimal immunity remain to be further explored. Here, an adjuvant platform STINGsome is described, composed of a STING agonist and pH-switchable IP9 liposomes, to simulate viral infection via STING activation and necroptosis. STINGsomes function as an efficient adjuvant to elicit broad and potent immune responses against multiple SARS-CoV-2 VOCs (Omicron BA.1, BA.2, BA.3, BA.4/5) and a monkeypox virus. More importantly, the adjuvant properties of STINGsomes can be tuned by simply adjusting the IP9 percentage, owing to distinct kinetics from local release to lymph node stimulation. Thus, this study provides a relatively simple strategy to adapt an adjuvant platform to different pathogenic antigens, ultimately achieving optimal protective responses.
研究领域:
免疫学
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病毒学
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药学
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生物技术
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Mingzhi Li,Xiaojun Huang,Jiajia Wen,Shikang Chen,Xincheng Wu,Wanning Ma,Steve W. Cui,Mingyong Xie,Shaoping Nie
The law and mechanism of the interaction between polysaccharides and pattern recognition receptors (PRRs) has been unclear. Herein, three glucomannans with different structures were selected to explore the universal mechanism for PRRs to recognize glucomannans. Screening results showed that the silence of TLR4 but not TLR2 severely blocked the production of inflammatory cytokines and the transduction of signal pathways. In-depth results revealed that the participation of myeloid differentiation protein 2 (MD2) and CD14 and the dimerization of the TLR4-MD2 complex were required for glucomannan-activated TLR4 signal transduction . Mannose receptor (MR) was also engaged in glucomannan-induced respiratory burst, endocytosis , and inflammatory signaling pathways in a spleen tyrosine kinase-dependent manner. The internalization of glucomannans into the cytoplasm by MR directly initiated complex intracellular signaling cascades. Finally, molecular docking characterized the binding energy and binding sites between glucomannans and multiple receptors from other perspectives. The essence of glucomannans recognized by PRRs was the non-covalent interaction of multiple receptors and the subsequent transmission of the signal cascade was triggered in a multi-channel and cooperative manner. As a result, the hypothesis that “Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response” was proposed to outline these meaningful phenomena.
研究领域:
免疫学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2024
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IF 5.7
Rikun Cui,Zhenzhao Wang,Linna Li,Lili Liu,Zhen Li,Xingtong Liu,Tingting Chen,Ayesha Rauf,Xiaofeng Kang,Yanli Guo
Background Enantiodiscrimination of chiral drugs is critical for understanding physiological phenomena and ensuring medical safety. Although enantiomers of these drugs share identical physicochemical properties, they exhibit significant differences in pharmacodynamic , pharmacokinetic , and toxicological properties due to the differences in their three-dimensional shapes. Therefore, the development of effective methods for chiral recognition is of great significance and has been a hot topic in chemo/biological studies. Results In this study, we designed a recognition receptor comprising a α-hemolysin (α-HL) nanopore and sulfobutyl ether-β-cyclodextrin (SBEβCD) for identifying the enantiomers of the antidepressant duloxetine at the single-molecule level. Chiral molecules were discriminated based on the different current blockages within the recognition receptor. The results indicated a strong interaction between R -duloxetine and the recognition receptor. By combining the experimental data and molecular docking results, we explored the recognition mechanism of the designed nanopore recognition receptor for chiral drug molecules. It was found that hydrophobic and electrostatic interactions play key roles in chiral recognition. Additionally, by comparing the binding kinetics of enantiomers to cyclodextrins in confined nanospace and bulk solution, we found that enantiomeric identification was better facilitated in the confined nanospace. Finally, the enantiomeric excess ( ee ) of the enantiomeric duloxetine mixture was measured using this recognized receptor. Significance This strategy has the advantages of low cost, high sensitivity, and no need for additional derivative modifications, providing a new perspective on the development of chiral recognition sensors with excellent enantioselectivity in drug design , pharmaceuticals, and biological applications.
研究领域:
分析化学
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纳米技术
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药学
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生物技术
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产品关联
DOI
PubMed
高影响因子
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