Trichomonas vaginalis Exosomes Deliver Cargo to Host Cells and Mediate Host:Parasite Interactions

被引:207
作者
Twu, Olivia [1 ]
de Miguel, Natalia [2 ,3 ]
Lustig, Gila [2 ]
Stevens, Grant C. [2 ]
Vashisht, Ajay A. [4 ]
Wohlschlegel, James A. [1 ,4 ]
Johnson, Patricia J. [1 ,2 ]
机构
[1] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA
[2] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA
[3] CONICET UNSAM, IIB INTECH, Buenos Aires, DF, Argentina
[4] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90024 USA
基金
美国国家卫生研究院;
关键词
OUTER-MEMBRANE VESICLES; EPITHELIAL-CELLS; DIFFERENTIAL EXPRESSION; STRUCTURAL ORGANIZATION; TETRASPANIN PROTEINS; PROTEOMICS ANALYSIS; CYSTEINE PROTEASES; IMMUNE-RESPONSES; GENOME SEQUENCE; B-LYMPHOCYTES;
D O I
10.1371/journal.ppat.1003482
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T. vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host: parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite: parasite communication and host cell colonization.
引用
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页数:14
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共 77 条
[1]   Trichomonas vaginalis Genital Infections: Progress and Challenges [J].
Bachmann, Laura H. ;
Hobbs, Marcia M. ;
Sena, Arlene C. ;
Sobel, Jack D. ;
Schwebke, Jane R. ;
Krieger, John N. ;
McClelland, R. Scott ;
Workowski, Kimberly A. .
CLINICAL INFECTIOUS DISEASES, 2011, 53 :S160-S172
[2]   Trichomonas vaginalis lipophosphoglycan mutants have reduced adherence and cytotoxicity to human ectocervical cells [J].
Bastida-Corcuera, FD ;
Okumura, CY ;
Colocoussi, A ;
Johnson, PJ .
EUKARYOTIC CELL, 2005, 4 (11) :1951-1958
[3]   Exosome Secretion: Molecular Mechanisms and Roles in Immune Responses [J].
Bobrie, Angelique ;
Colombo, Marina ;
Raposo, Graca ;
Thery, Clotilde .
TRAFFIC, 2011, 12 (12) :1659-1668
[5]   In vivo and in vitro protein solubility assays using split GFP [J].
Cabantous, Stephanie ;
Waldo, Geoffrey S. .
NATURE METHODS, 2006, 3 (10) :845-854
[6]   Exosomes/microvesicles as a mechanism of cell-to-cell communication [J].
Camussi, Giovanni ;
Deregibus, Maria C. ;
Bruno, Stefania ;
Cantaluppi, Vincenzo ;
Biancone, Luigi .
KIDNEY INTERNATIONAL, 2010, 78 (09) :838-848
[7]   Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis [J].
Carlton, Jane M. ;
Hirt, Robert P. ;
Silva, Joana C. ;
Delcher, Arthur L. ;
Schatz, Michael ;
Zhao, Qi ;
Wortman, Jennifer R. ;
Bidwell, Shelby L. ;
Alsmark, U. Cecilia M. ;
Besteiro, Sebastien ;
Sicheritz-Ponten, Thomas ;
Noel, Christophe J. ;
Dacks, Joel B. ;
Foster, Peter G. ;
Simillion, Cedric ;
Van de Peer, Yves ;
Miranda-Saavedra, Diego ;
Barton, Geoffrey J. ;
Westrop, Gareth D. ;
Mueller, Sylke ;
Dessi, Daniele ;
Fiori, Pier Luigi ;
Ren, Qinghu ;
Paulsen, Ian ;
Zhang, Hanbang ;
Bastida-Corcuera, Felix D. ;
Simoes-Barbosa, Augusto ;
Brown, Mark T. ;
Hayes, Richard D. ;
Mukherjee, Mandira ;
Okumura, Cheryl Y. ;
Schneider, Rachel ;
Smith, Alias J. ;
Vanacova, Stepanka ;
Villalvazo, Maria ;
Haas, Brian J. ;
Pertea, Mihaela ;
Feldblyum, Tamara V. ;
Utterback, Terry R. ;
Shu, Chung-Li ;
Osoegawa, Kazutoyo ;
de Jong, Pieter J. ;
Hrdy, Ivan ;
Horvathova, Lenka ;
Zubacova, Zuzana ;
Dolezal, Pavel ;
Malik, Shehre-Banoo ;
Logsdon, John M., Jr. ;
Henze, Katrin ;
Gupta, Arti .
SCIENCE, 2007, 315 (5809) :207-212
[8]   Methods for cultivation of luminal parasitic protists of clinical importance [J].
Clark, CG ;
Diamond, LS .
CLINICAL MICROBIOLOGY REVIEWS, 2002, 15 (03) :329-+
[9]   Lipid raft-associated protein sorting in exosomes [J].
de Gassart, A ;
Géminard, C ;
Février, B ;
Raposo, G ;
Vidal, M .
BLOOD, 2003, 102 (13) :4336-4344
[10]   Proteome Analysis of the Surface of Trichomonas vaginalis Reveals Novel Proteins and Strain-dependent Differential Expression [J].
de Miguel, Natalia ;
Lustig, Gil ;
Twu, Olivia ;
Chattopadhyay, Arnab ;
Wohlschlegel, James A. ;
Johnson, Patricia J. .
MOLECULAR & CELLULAR PROTEOMICS, 2010, 9 (07) :1554-1566