An exosome-based secretion pathway is responsible for protein export fromLeishmaniaand communication with macrophages
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Open Access
- 15 March 2010
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 123 (6), 842-852
- https://doi.org/10.1242/jcs.056465
Abstract
Specialized secretion systems are used by numerous bacterial pathogens to export virulence factors into host target cells. Leishmania and other eukaryotic intracellular pathogens also deliver effector proteins into host cells; however, the mechanisms involved have remained elusive. In this report, we identify exosome-based secretion as a general mechanism for protein secretion by Leishmania, and show that exosomes are involved in the delivery of proteins into host target cells. Comparative quantitative proteomics unambiguously identified 329 proteins in Leishmania exosomes, accounting for >52% of global protein secretion from these organisms. Our findings demonstrate that infection-like stressors (37 degrees C +/- pH 5.5) upregulated exosome release more than twofold and also modified exosome protein composition. Leishmania exosomes and exosomal proteins were detected in the cytosolic compartment of infected macrophages and incubation of macrophages with exosomes selectively induced secretion of IL-8, but not TNF-alpha. We thus provide evidence for an apparently broad-based mechanism of protein export by Leishmania. Moreover, we describe a mechanism for the direct delivery of Leishmania molecules into macrophages. These findings suggest that, like mammalian exosomes, Leishmania exosomes function in long-range communication and immune modulation.This publication has 40 references indexed in Scilit:
- The impact of vector-mediated neutrophil recruitment on cutaneous leishmaniasisCellular Microbiology, 2009
- Proteomic and immunologic analyses of brain tumor exosomesThe FASEB Journal, 2008
- AmiGO: online access to ontology and annotation dataBioinformatics, 2008
- Vesicular transport inHistoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetesCellular Microbiology, 2008
- Ceramide Triggers Budding of Exosome Vesicles into Multivesicular EndosomesScience, 2008
- Changes in protein expression during honey bee larval developmentGenome Biology, 2008
- Extracellular Vesicles Produced by Cryptococcus neoformans Contain Protein Components Associated with VirulenceEukaryotic Cell, 2008
- Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivoBlood, 2007
- Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cellsNature, 2007
- The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans The Journal of cell biology, 2006