| Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. | |
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MedLine Citation:
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PMID: 20881185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the properties of leishmania exosomes with respect to influencing innate and adaptive immune responses. Exosomes from Leishmania donovani modulated human monocyte cytokine responses to IFN-γ in a bimodal fashion by promoting IL-10 production and inhibiting that of TNF-α. Moreover, these vesicles were inhibitory with respect to cytokine responses (IL-12p70, TNF-α, and IL-10) by human monocyte-derived dendritic cells. Exosomes from wild-type (WT) L. donovani failed to prime monocyte-derived dendritic cells to drive the differentiation of naive CD4 T cells into IFN-γ-producing Th1 cells. In contrast, vesicles from heat shock protein (HSP)100(-/-) L. donovani showed a gain-of-function and proinflammatory phenotype and promoted the differentiation of naive CD4 lymphocytes into Th1 cells. Proteomic analysis showed that exosomes from WT and HSP100(-/-) leishmania had distinct protein cargo, suggesting that packaging of proteins into exosomes is dependent in part on HSP100. Treatment of C57BL/6 mice with WT L. donovani exosomes prior to challenge with WT organisms exacerbated infection and promoted IL-10 production in the spleen. In contrast, HSP100(-/-) exosomes promoted spleen cell production of IFN-γ and did not adversely affect hepatic parasite burdens. Furthermore, the proparasitic properties of WT exosomes were not species specific because BALB/c mice exposed to Leishmania major exosomes showed increased Th2 polarization and exacerbation of disease in response to infection with L. major. These findings demonstrate that leishmania exosomes are predominantly immunosuppressive. Moreover, to our knowledge, this is the first evidence to suggest that changes in the protein cargo of exosomes may influence the impact of these vesicles on myeloid cell function. |
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Authors:
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Judith Maxwell Silverman; Joachim Clos; Eva Horakova; Adele Y Wang; Martina Wiesgigl; Isabelle Kelly; Miriam A Lynn; W Robert McMaster; Leonard J Foster; Megan K Levings; Neil E Reiner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-29 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-21 Completed Date: 2010-11-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 5011-22 Citation Subset: AIM; IM |
Affiliation:
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Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptive Immunity
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immunology* Animals Antigens, Protozoan / immunology Cell Differentiation / immunology Cell Separation Cytokines / biosynthesis, immunology Dendritic Cells / immunology, microbiology* Electrophoresis, Gel, Two-Dimensional Exosomes / immunology* Flow Cytometry Heat-Shock Proteins / immunology, metabolism Humans Immunity, Innate / immunology* Leishmania donovani / immunology*, metabolism Leishmaniasis / immunology Lymphocyte Activation / immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Monocytes / immunology, microbiology* Protozoan Proteins / immunology, metabolism Reverse Transcriptase Polymerase Chain Reaction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization T-Lymphocytes / cytology, immunology |
| Grant Support | |
ID/Acronym/Agency:
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MOP-57834//Canadian Institutes of Health Research; MOP-7399//Canadian Institutes of Health Research; MOP-77688//Canadian Institutes of Health Research; MOP-84582//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Protozoan; 0/ClpB protein, Leishmania; 0/Cytokines; 0/Heat-Shock Proteins; 0/Protozoan Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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