PATHOGEN-‐DERIVED EVs
CHAIRS
ANTONIO MARCILLA Departament de Biologia Cel.lular i Parasitologia,
Universitat de València, Valencia, Spain [email protected]
HERNANDO A DEL PORTILLO ICREA at Barcelona Centre for InternaJonal Health
Research – CRESIB, Barcelona, Spain [email protected]
ISEV 2014, RoRerdam April 30th – May 3rd 2014
O1C-‐013 TRYPANOSOMA CRUZI-‐DERIVED MICROVESICLES TRIGGER DISTINCT STRAIN-‐SPECIFIC PROINFLAMMATORY ACTIVITY VIA TLR2 R. Soares 1,* K. Ribeiro 2, C. Miranda 2, P. Nogueira 1, A. C. Silveira 1, O. MarKns-‐Filho 1, A. C. Torrecilhas 2 1Laboratório de Biomarcadores de DiagnósKco e Monitoração, Centro de Pesquisas René Rachou, Belo Horizonte, 2Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, Brazil O1C-‐014 Biogenesis Mechanisms of Bacterial Vesicles M. Kuehn 1,* 1Biochemistry, Duke University Medical Center, Durham, United States O1C-‐015 Membrane vesicles released from Uropathogenic Escherichia coli transport an RNA cargo C. Blenkiron 1,* , D. Simonov 1, A. MUTHUKARUPPAN 1, P. Tsai 1, S. Green 1, C. Print 1, S. Swi` 1, A. Phillips 1 1Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand O1C-‐016 Extracellular vesicle-‐mimeKc nanovesicles derived from bacterial protoplast as next generaKon vaccine delivery system for effecKve prevenKon of infecKous diseases O. Y. Kim 1,* , S. J. Choi 1, K.-‐S. Park 1, S. C. Jang 1, J. Lötvall 2, Y.-‐K. Kim 1, Y. S. Gho 1 1Life Science, POSTECH, Po Hang, Korea, Republic Of, 2Kre`ing Research Centre, Internal Medicine, University of Gothenburg, Gothenburg, Sweden O1C-‐017 ConservaKon of exosome funcKon during viral infecKon in Drosophila melanogaster C. Kerr 1,* , L. Foster 1, E. Jan 1 1Biochemistry and Molecular Biology, University of BriKsh Columbia, Vancouver, Canada
INTRODUCTORY REMARKS
Hernando A del PorKllo, PhD
“SomeJme, about 150,000 years ago, Homo sapiens emerged in eastern Africa and spread throughout the world, possibly in several waves, unJl 15,000 years ago. At the end of the Ice Age humans had migrated to and inhabited virtually the whole of the face of the Earth, bringing some parasites with them and collecJng others on the way.
During our relaJvely short history on Earth, humans have acquired an amazing number of parasites, about 300 species of helminth worms and over 70 species of protozoa . Many of these are rare and accidental parasites, but we sJll harbor about 90 relaJvely common species, of which a small proporJon cause some of the most important diseases in the world.
So vast is the field of human parasitology, and so many and far-‐reaching the discoveries made, that it is not possible to do jusJce to the whole subject. Therefore; only the most significant aspects and the most important parasites are considered under two major headings, the helminth worms and the protozoa”.
COX F.E.G. CLINICAL MICROBIOLOGY REVIEWS, Oct. 2002, p. 595–612
HISTORY OF HUMAN PARASITOLOGY
InfecJous and ParasiJc Diseases are the Second Cause of Mortality in the World
Source: TropiKA.net
PARASITIC DISEASES ARE GLOBALLY DISTRIBUTED
Hotez et al. 2008 J Clin Inv
Worms are responsible for millions of clinical cases
Threadgold, 1963 Quart. J. micr. Sci.
FIG. 3 (plate), A, cuJcular surface, showing the electron-‐dense zone of invaginaJons, pinocytoJc vacuoles, and small vesicles.
E. caproni
100 nm 100 nm
F. hepa.ca
56%
SECRETOME ECV
In summary, although the secreJon of exosome-‐like vesicles has been demonstrated in several organisms, we have shown the producJon of these structures by parasiJc helminths for the first Jme.
Bernal et al., 2014 J Proteomics
PARASITIC PROTOZOA AND ASSOCIATED DISEASES
hRp://www.pathobio.sdu.edu.cn/sdjsc/engparabook/ch077.htm
www.stanford.edu
Trichomona vaginalis is the causaKve agent of trichomoniasis, and is the most common pathogenic protozoan infecKon of humans in industrialized countries The WHO has esKmated that 275 million cases of infecKon are acquired annually worldwide.
PreincubaKon with exosomes of a highly adherent strain increases adherence of a poorly adherent strain to Ects
TrypanosomaKds
source: hRps://www.msf.es/chagas/mainchallenges.html
COMPLEX LIFE CYCLE
P. falciparum
216 million clinical cases
650.000 deaths
P. vivax 2.85 billions of people at risk
70-‐320 millions of clinical cases yearly
Global distribuKon and endemicity of P. falciparum & P. vivax
source: hpp://www.learner.org/courses/biology/archive/images/1859.html
Neta-‐Regevski et al., Cell 2013
CommunicaKon between Parasites Results in DifferenKaKon to Sexual Stages and Transfer of DNA
Plasmodium vivax invades exclusively reKculocytes
Exosomes
Hypothesis: - Exosomes derived from Plasmodium vivax infected reticulocytes
contain parasite proteins and can modulate immune responses.
exosomes
MVB
Aikawa, Barnwell, Galinski. del PorKllo et al 2001 Nature
Exosomes+CpG immunization
Py XL Py XL Py XL
Immunized mice present sterile protecJon in subsequent infecJons
20 days 20 days parasitemia
P. yoelii 17XL NI
5 µg s.c. 10 µg s.c +CpG. rexPy
rexC rexPy rexC
MarKn-‐Jaular et al., 2011 PLoS One
PARASITES AND EVs
Barteneva et al., 2013 FronKers Cell Inf Microbiol
