Development of immunity-based strategy to manage bacterial infection is urgently needed in aquaculture due to the widespread of antibiotic-resistant bacteria. Phagocytosis serves as the first line defense in innate immunity that engulfs bacteria and restricts their proliferations and invasions. However, the mechanism underlying the regulation of phagocytosis is not fully elucidated and the way to boost phagocytosis is not yet explored. In this manuscript, we profiled the metabolomes of monocytes/macrophages isolated from Nile tilapia, prior and after phagocytosis on . Monocytes/macrophages showed a metabolic shift following phagocytosis. Interestingly, succinate was accumulated after phagocytosis and was identified as a crucial biomarker to distinguish before and after phagocytosis. Exogenous succinate increased the phagocytotic rate of monocytes/macrophages in a dose-dependent manner. This effect was dependent on the TCA cycle as the inhibitor of malonate that targets succinate dehydrogenase abrogated the effect. Meanwhile, exogenous succinate regulated the expression of genes associated with innate immune and phagocytosis. In addition, succinate-potentiated phagocytosis was applicable to both gram-negative and -positive cells, including , and . Our study shed light on the understanding of how modulation on host's metabolism regulates immune response, and this can be a potent therapeutic approach to control bacterial infections in aquaculture.
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http://dx.doi.org/10.3389/fmolb.2021.644957 | DOI Listing |
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January 2025
Cancer Hospital of Dalian University of Technology, Dalian University of Technology, Shenyang, 110042, China.
Glioblastoma (GBM), the most malignant brain tumor with high prevalence, remains highly resistant to the existing immunotherapies due to the significant immunosuppression within tumor microenvironment (TME), predominantly manipulated by M2-phenotypic tumor-associated macrophages (M2-TAMs). Here in this work, an M2-TAMs targeted nano-reprogrammers, MG5-S-IMDQ, is established by decorating the mannose molecule as the targeting moiety as well as the toll-like receptor (TLR) 7/8 agonist, imidazoquinoline (IMDQ) on the dendrimeric nanoscaffold. MG5-S-IMDQ demonstrated an excellent capacity of penetrating the blood-brain barrier (BBB) as well as selectively targeting M2-TAMs in the GBM microenvironment, leading to a phenotype transformation and function restoration of TAMs shown as heightened phagocytic activity toward tumor cells, enhanced cytotoxic effects, and improved tumor antigen cross-presentation capability.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Evergreen World ADHC, Westminster, CA 92844, USA.
As the organism ages, there is a decline in effective energy supply, and this retards the ability to elaborate new proteins. The consequences of this are especially marked in the gradual decline in brain function. The senescence of cells and their constituent organelles is ultimately the cause of aging of the entire nervous system.
View Article and Find Full Text PDFDiagnostics (Basel)
December 2024
Department of Pathology, Faculty of Medicine, Gaziantep University, 27410 Gaziatep, Turkey.
Renal cell carcinoma is an aggressive form of kidney cancer, contributing to an estimated 138,000 deaths globally in 2017. Traditional treatments like chemotherapy and radiation are generally considered ineffective. Additionally, CD47 has been identified as a crucial tumor antigen involved in the development and progression of various cancers, including renal cell carcinoma.
View Article and Find Full Text PDFPolymers (Basel)
December 2024
Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, 119991 Moscow, Russia.
Macrophage (Mph) polarization and functional activity play an important role in the development of inflammatory lung conditions. The previously widely used bimodal classification of Mph into M1 and M2 does not adequately reflect the full range of changes in polarization and functional diversity observed in Mph in response to various stimuli and disease states. Here, we have developed a model for the direct assessment of Mph from bronchial alveolar lavage fluid (BALF) functional alterations, in terms of phagocytosis activity, depending on external stimuli, such as exposure to a range of bacteria (, and ).
View Article and Find Full Text PDFNat Commun
January 2025
Institute of Anatomy and Cell Biology, Saarland University, Homburg, Germany.
Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.
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