MicroRNAs are a family of regulatory molecules involved in many physiological processes, including differentiation and activation of cells of the immune system. We found that brainspecific miR-124 is expressed in microglia but not in peripheral monocytes or macrophages. When overexpressed in macrophages, miR-124 directly inhibited the transcription factor CCAAT/ enhancer-binding protein-α (C/EBP-α) and its downstream target PU.1, resulting in transformation of these cells from an activated phenotype into a quiescent CD45 low , major histocompatibility complex (MHC) class II low phenotype resembling resting microglia. During experimental autoimmune encephalomyelitis (EAE), miR-124 was downregulated in activated microglia. Peripheral administration of miR-124 in EAE caused systemic deactivation of macrophages, reduced activation of myelin-specific T cells and marked suppression of disease. Conversely, knockdown of miR-124 in microglia and macrophages resulted in activation of these cells in vitro and in vivo. These findings identify miR-124 both as a key regulator of microglia quiescence in the central nervous system and as a previously unknown modulator of monocyte and macrophage activation.MicroRNAs (miRNAs) belong to a family of small non-protein-coding RNAs that regulate expression of multiple target genes and are involved in many fundamental biological processes, such as embryonic development, cell proliferation, differentiation and apoptosis [1][2][3][4][5] . miRNAs promote degradation of mRNA or prevent translation of the target genes, and they can be viewed as endogenous mediators of RNA interference (RNAi) 1 . miRNAs have been identified as crucial regulators of differentiation of various cell types, © 2011 Nature America, Inc. All rights reserved. Correspondence should be addressed to H.L.W. (hweiner@rics.bwh.harvard.edu) and A.M.K. (akrichevsky@rics.bwh.harvard.edu).. 3 These authors contributed equally to this work. AUTHOR CONTRIBUTIONS E.D.P. performed all flow-cytometry assays, EAE experiments, experiments with chimeric, knockout and transgenic mice, in vivo injections of oligonucleotides, cell isolations, cell cultures, coculture assays and immunohistochemistry; collected and analyzed the data; and wrote the manuscript. T.V. performed in vitro transfections, miRNA and mRNA expression assays and data analysis, western blots, luciferase target validation assay, immunohistochemistry and in silico target prediction analysis and helped to write the manuscript. N.B. performed imaging cytometry. E.D.P. and A.M.K. conceived the project. E.D.P., T.V. and A.M.K. developed the hypothesis and designed the experiments. A.M.K. and H.L.W. discussed the hypothesis, helped with data interpretation, coordinated and directed the project and wrote the manuscript.Note: Supplementary information is available on the Nature Medicine website. COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests. 2,6 . Furthermore, deregulated expression of specific miRNAs is associated with many patholo...
Summary Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBC), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have pro-inflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.
Emiliania huxleyi is a model coccolithophore micro-alga that generates vast blooms in the ocean. Bacteria are not considered among the major factors influencing coccolithophore physiology. Here we show through a laboratory model system that the bacterium Phaeobacter inhibens, a well-studied member of the Roseobacter group, intimately interacts with E. huxleyi. While attached to the algal cell, bacteria initially promote algal growth but ultimately kill their algal host. Both algal growth enhancement and algal death are driven by the bacterially-produced phytohormone indole-3-acetic acid. Bacterial production of indole-3-acetic acid and attachment to algae are significantly increased by tryptophan, which is exuded from the algal cell. Algal death triggered by bacteria involves activation of pathways unique to oxidative stress response and programmed cell death. Our observations suggest that bacteria greatly influence the physiology and metabolism of E. huxleyi. Coccolithophore-bacteria interactions should be further studied in the environment to determine whether they impact micro-algal population dynamics on a global scale.DOI: http://dx.doi.org/10.7554/eLife.17473.001
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