Translational research : the journal of laboratory and clinical medicine
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Lung inflammation is tightly controlled to balance microbial clearance with the tissue damage that accompanies this response. Bacterial pathogens including Streptococcus pneumoniae (S. pneumoniae) modulate immune regulation by promoting secretion of the anti-inflammatory cytokine IL-10. The important cellular sources of IL-10 that impact protection against different bacterial infections are not well characterized. ⋯ Direct transfer of wild-type NK cells into the lungs of IL-10-deficient mice drives bacterial expansion, identifying NK cells as a critical source of IL-10 promoting S. pneumoniae infection. The S. pneumoniae virulence protein Spr1875 was found to elicit NK cell IL-10 production in purified cells and in the lungs of live animals. These findings reveal therapeutic targets to combat bacterial-driven immune regulation in the lung.
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Retracted Publication
Transfer of microRNA-221 from mesenchymal stem cell-derived extracellular vesicles inhibits atherosclerotic plaque formation.
Mesenchymal stem cells (MSCs) have emerged as a cell-based therapy in many diseases including atherosclerosis (AS) due to their capability of immunomodulation and tissue regeneration. However, the pathway for MSCs' antiatherosclerotic activity remains to be elucidated. Here, we test the hypothesis that microRNA-221 (miR-221) from MSC-derived extracellular vesicles (EVs) alleviates AS. ⋯ Human bone marrow mesenchymal stem cell -derived EVs carrying miR-221 were internalized by human arterial smooth muscle cells and transferred their miR-221 contents to downregulate the target gene NAT1. Injection of miR-221-containing EVs inhibited lipid deposition in AS mice, in part by downregulating NAT1. The present study provides evidence that miR-221 shuttled by MSC-derived EVs can inhibit atherosclerotic plaque formation in AS model mice, suggesting that miR-221 may serve as a target for improving MSC-based therapeutic strategy against AS.
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In the past decade knowledge has expanded regarding the importance of the gut microbiota in maintaining intestinal homeostasis and overall health. During this same time, we have also gained appreciation for the role of the gut-liver axis in the development of liver diseases. ⋯ With advances in technology to investigate the gut microbiome and metabolome, we are now beginning to delineate alcohol's effects on the gut microbiome in relation to liver disease. This review presents our current understanding on the role of the gut microbiota during alcohol exposure, and various therapeutic attempts that have been made to reprogram the gut microbiota with the goal of alleviating alcoholic-related liver disease.
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The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed "dysbiosis," often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. ⋯ These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and preclinical therapies for treating age-related dysbiosis.