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We screened innate immunostimulant-producing bacteria using a silkworm muscle contraction assay, and isolated Rhizobium sp. strain M2 from soil. We purified the innate immunostimulant from strain M2, and characterized the chemical structure by nuclear magnetic resonance spectroscopy and chemical analyses. The innate immunostimulant (M2 EPS) comprised glucose, galactose, pyruvic acid, and succinic acid with a molar ratio of 6.8:1.0:0.9:0.4, and had a succinoglycan-like high molecular-weight heteropolysaccharide structure. To determine the structural motif involved in the innate immunostimulating activity, we modified the M2 EPS structure chemically, and found that the activity was increased by removal of the succinic and pyruvic acid substitutions. Strong acid hydrolysis completely inactivated the M2 EPS. Unmasking of the β-1,3/6-glucan structure of the side-chain by deacylation and depyruvylation may enhance the innate immune-stimulating activity of M2 EPS. These findings suggest that the succinoglycan-like polysaccharide purified from strain M2 has innate immune-stimulating activity, and its glycan structure is necessary for the activity.
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http://dx.doi.org/10.5582/ddt.2017.01045 | DOI Listing |
Adv Mater
September 2025
Department of Neurosurgery, Qilu Hospital and Shandong Key Laboratory of Brain Health and Function Remodeling, Institute of Brain and Brain-Inspired Science, Jinan Microecological Biomedicine Shandong Laboratory, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong,
Innate immunity is crucial in orchestrating the brain immune response, however, glioblastoma multiforme (GBM) has evolved sophisticated mechanisms to evade innate immune surveillance, posing significant challenges for current immunotherapies. Here, a therapeutic strategy is reported that aims at reactivating innate immune responses in GBM via targeted induction of mitochondrial stress, thereby enhancing tumor immunogenicity. Specifically, innate immune-stimulating nanoparticles (INSTNA) are developed, encapsulating positively charged iridium-based complexes (Ir-mito) and small interfering RNA against Methylation-Controlled J protein (si-MCJ) to attenuate mitochondrial respiration.
View Article and Find Full Text PDFUnlabelled: Merkel Cell Polyomavirus (MCPyV) is an oncogenic human polyomavirus that latently infects most adults. Although the causative link between MCPyV and Merkel Cell Carcinoma (MCC) is well established, the molecular mechanisms that govern viral latency and prevent oncogenic progression remain poorly understood. We previously reported that the MCPyV early region protein ALTO is a key modulator of the STING-TBK1 signaling axis, enabling the virus to co-opt host innate immune pathways to suppress excessive viral replication and promote latency over transformation.
View Article and Find Full Text PDFVaccines (Basel)
July 2025
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Background/objectives: Freund's adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund's adjuvant (CFA) involve the mechanisms of trained immunity (TI).
Methods: We examined bone marrow cells (BMCs) isolated from CFA-immunized A/J mice to address this question.
Recently, rapidly evolving STING-based immunotherapies have offered novel therapeutic options for various cancer types. However, systemic administration of STING agonists raises safety concerns, and intratumoral injection is constrained by tumor accessibility. Herein we developed an immune-stimulating antibody conjugate (ISAC) that links STING agonists to antibodies that target HER2-positive tumor cells via a cleavable linker.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
National Engineering Research Center for the Emergency Drug, Academy of Military Medical Sciences, Beijing, 100850, China.
Immune-stimulating antibody conjugate (ISACs) incorporating STING agonists as payloads leverage both the targeting capability of the Fab region and the Fc region-mediated tumor antigen-dependent immune activation. Herein, a novel class of ISACs is reported, generated by engineering a quaternary ammonium-cleavable linker to conjugate diABZI STING agonist 3 (dSA3) with the HER2-targeting antibody Trastuzumab. The optimized ISAC (TZ-dSA3-12) demonstrated high potency, stability, enhanced solubility, and reduced off-target toxicity.
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