Martin Olivier
Professor
Currently not accepting students.
- Member of听黑料社 International TB Centre (RI-MUHC)
Leishmania exosomes: Role in transmission and propagation within its mammalian host
Over the last 20 years, our research have permitted to reveal that exosomes/extracellular vesicles (EVs) released by Leishmania parasite enriched the metalloprotease GP63 -the main virulence factor of this pathogen- and they rapidly inactivate host microbicidal and innate inflammatory responses favouring survival of the parasite and its propagation (review in Cellular Immunology S0008-8749 (16) 30062-4 (2016)). In addition, we further found that it can very effectively hijack the NLRP3 Inflammasome complex by cleaving several critical members of this sensor complex (PLoS Neglected Tropical Diseases 9 (6): e0003868 (2015)). Of utmost importance, we reported the first observation that a pathogen can release exosomes within its insect vector and to be co-egested during the blood meal to the mammalian host, favouring the infectious process (see Cell Reports (13: 957-967 (2015); Recommended in Faculty of F1000Prime, Special Significance). As shown in some of the papers reported under, our work on EVs led to establish their critical roles in the context of infection, immunity and inflammation, paving the way to the development of new therapies and diagnostics.
Study of PTP Inhibitors and their Impact on Immune Response and Control over Leishmania
Journal of Biological Chemistry, 273: 13944-13949 (1998); European Journal of Immunology 30: 2555-2564 (2000). In these papers are reported for the first time that a protein tyrosine phosphatase (PTP) inhibitors (peroxovanadium (pV)) can protect mice against visceral and cutaneous leishmaniasis. This study represents the first report where an inhibitor of phosphatases can change the course of an infection. We also provided evidence that some of these pV compounds can directly affect the parasitic growth, as well as to prime phagocytes for enhance responsiveness toward cytokine stimulation as reflected by increased nitric oxide generation. Our results permitted to conclude that pV-mediated protection in vivo against leishmaniasis is in part NO dependent and to involve exacerbated neutrophils-mediated inflammatory responses having an important impact on the progression of leishmaniasis. This study importantly revealed that these pV compounds are very powerful immunomodulators that could be use ultimately in different experimental and, even one day, clinical contexts (i.e. Since then we further showed their capacity to control cancer, asthma and cerebral malaria).
Role of the PTPs and Parasite GP63 Protease in Leishmania Progression in vitro & in vivo
Science Signaling, 29(90), ra58. Pages 1-12 (2009) (Review in Faculty of 1000; Must read (6.0))
European Journal of Immunology, 29: 3737-3744 (1999); Eur. J. Immunol. 31: 3185-3196 (2001). We have reported the first evidence that Leishmania can rapidly induce host cell PTP SHP-1 inactivating JAK2-dependent signaling pathways and to be a critical strategy used by Leishmania to deactivate macrophage functions. Thereafter using SHP-1 deficient mice, we have confirmed the pivotal role played by SHP-1 in the regulation of Leishmania infection and progression. More recently, we have discovered that the Leishmania metallo-protease GP63 is a critical virulence factors concurring to activate host cell PTPs (SHP-1, PTP1B, TCPTP) and that the PTP1B is also an important player in the early inactivation process triggered by Leishmania but not sufficient to fully control disease progression. We suspect that activation of nuclear TCPTP could play a crucial in leishmaniasis.
M.A. Gomez, I. Contreras, M. Halle, M.L. Tremblay, R.W. McMaster and M. Olivier.
The major surface protease of Leishmania is implicated in the modulation of macrophage protein tyrosine phosphatases.
Science Signaling 2 (90), ra58. Pages 1-12 (2009). (Faculty of 1000; Must read (6.0))
I. Contreras-Garcia, M.A. Gomez, O. Nguyen, M.T. Shio, R.W. McMaster and M. Olivier.
Leishmania-induced inactivation of the macrophage transcription factor AP-1 is mediated by the parasite metalloprotease GP63
PLoS Pathogens E-pub Oct 15th (2010).
M. Jaramillo, M.A. Gomez, O. Larsson, M.T. Shio, I. Toposorovic, I. Contreras, R. Luxenburg, A. Rosenfeld, R. Colina, R.W. McMaster, M. Olivier*, M. Costa-Mattioli* and N. Sonenberg*.听Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection.
Cell Host & Microbes 9(4):331-41 (2011). *Equal co-corresponding authors.
M. Olivier. Host-Pathogen Interaction : Culprit within a culprit.
Nature 471: 173-174 (2011).
M. Olivier, K. Van Den Ham, M.T. Shio, F.A. Kassa and S. Fougeray.
Malarial Pigment Hemozoin and Innate Inflammatory Response.
Frontiers in Immunology 5:25. doi: 10.3389/fimmu.2014.00025 (2014).
V.D. Atayde, H.A. Suau, S. Townshend, K. Hassani, S. Kamhawi and M. Olivier. In vivo Secretion of Exosomes by Sandfly-Residing Leishmania Parasites.
Cell Reports 13: 957-967 (2015). (Faculty of F1000Prime, Special Significance)
K. Van den Ham, L. Smith, M. Richer and M. Olivier. Protein tyrosine phosphatase activity is required for liver injury and pathogenic T cell trafficking during Plasmodium berghei Anka 颈苍蹿别肠迟颈辞苍.听Scientific Reports 7(1):5478. doi: 10.1038/s41598-017-05609-1. (2017)
V. D. Atayde, A. da Silva Lira Filho, V. Chaparro, A. Zimmermann, C. Martel, M. Jaramillo and M. Olivier. Exploitation of the Leishmania exosomal pathway by Leishmania RNA Virus 1.听Nature Microbiology 4(4) : 714-723. (doi: 10.1038/s41564-018-0352-y) (2019)
E. Heirwegh, E. MacLean, J. He, S. Kamhawi, S.M. Sagan and M. Olivier.
Sandfly Fever Sicilian Virus-Leishmania major co-infection modulates innate inflammatory response favoring myeloid cell infections and skin hyperinflammation.
PLoS Neglected Tropical Diseases doi.org/10.1371/journal.pntd.0009638 (2021)
da Silva Lira Filho, E. Francisco Fajardo, K.P Chang, P. Cl茅ment and M. Olivier. Leishmania Exosomes Containing GP63 is Essential for Enhance CutaneousLeishmaniasis upon co-inoculation of Leishmania amazonensis and its exosomes.听Frontiers in Cellular and Infection Microbiology doi: 10.3389/fcimb.2021.709258 (2022)
N. Douanne, G. Dong, A. Amin, L. Bernardo, M. Blanchette, D. Langlais, M. Olivier* and C. Fernandez-Prada*. Leishmania parasites exchange drug-resistance genes through extracellular vesicles.听Cell Reports doi.org/10.1016/j.celrep.2022.111121 (2022). *Equal co-corresponding authors
A. Lafleur and M. Olivier. Viral endosymbiotic infection of protozoan parasites: How it influences the development of cutaneous leishmaniasis.
PLoS Pathogens 18(11): e1010910. (2022)
C. Fernandez-Becerra*, P. Xander; H. Del Portillo, N. Cortes-Serra, M. Gualdron-Lopez, M. I Ramirez, P. Meneghetti, N. Lozano, N. Regev-Rudzki, P. Abou Karam, D. Alfandari, I. Rosenhek-Goldian, Z. Porat, R.P. Soares, A. Costa Oliveira, G. Dong, S. Rafati, M. Shokouhy, A. Cordeiro-da-Silva, N. Santarem, C. Fernandez Prada, D. Bernal, A. Marcilla, S. Schenkman, M. Olivier* and A. C. Torrecilhas*. The parameters guidelines for the purification characterization of the extracellular vesicles release from parasites.
Journal of Extracellular Biology doi.org/10.1002/jex2.117 (2023).
*Equal co-corresponding authors
A. Vucetic, A. Lafleur, M. Cot茅, D. Kobasa, M. Chan, F. Alvarez, C. Piccirillo, G. Dong and M. Olivier. 鈥淓xtracellular vesicles storm鈥� during the course of ebola virus infection in primates.听Frontiers in Cellular and Infection Microbiology doi.org/10.3389/fcimb.2023.1275277 (2023)
M. Leroux, A. Lafleur, C. Villalba-Guerrero, M. Beaulieu, A. Brito Lira and M. Olivier. Extracellular vesicles in parasitic protozoa: Impact of Leishmania exosomes containing Leishmania RNA virus 1 (LRV1) on Leishmnania infectivity and disease progression. Current Topics in Membranes (2024)
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