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Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2018
Renseignements relatifs à l’Unité de Recherche :
Label et intitulé :
Institut Pasteur – Unité de Pathogénie Microbienne Moléculaire / Inserm 1202
28, rue du Dr. Roux 75724 Paris Cedex 15
Nom et prénom du Directeur : Pr. Sansonetti, Philippe
Téléphone : 01 45 68 83 42
Télécopie : 01 45 68 89 53
Courriel: [email protected]
Renseignements relatifs à l’Equipe :
Nom de l’Equipe d’Accueil : Infection Bactérienne et Immunité
Nom et prénom du responsable : Marteyn Benoit
Qualité du responsable : chercheur Inserm (CR1)
Téléphone : 01 45 68 83 08
Télécopie : 01 45 68 89 53
Courriel : [email protected]
Renseignements relatifs au sujet de thèse :
Nom et prénom du Directeur de thèse (HDR) : Marteyn, Benoit (soutenance HDR le 16 juin 2017)
Qualité : CR1
Téléphone : 01 45 68 83 08
Télécopie : 01 45 68 89 53
Courriel : [email protected]
Titre du sujet proposé :
Modulation par l’oxygène de l’activation et de la mort des neutrophiles au cours de l’infection par
Shigella
Oxygen-dependent modulation of neutrophils activation and cell death during Shigella infection
Département (cocher le département correspondant au sujet de thèse qui n’est pas obligatoirement le
vôtre) :
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Biologie Cellulaire et moléculaire, Physiologie et Physiopathologie
Immunologie
Développement Génétique Neurobiologie et Vieillissement
Infectiologie, Microbiologie
Summary
Neutrophils are the most abundant immune cell population recruited upon Shigella infection. We
developed original strategies to study neutrophils’ physiology and antimicrobial functions, which will be
exploited in this project. Since neutrophils face various oxygen levels during their lifecycle in the bone
marrow, in the bloodstream and within tissues infected by Shigella, we will evaluate how oxygen
exposure modulates their antimicrobial functions and survival in vitro and in vivo.
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Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2087
Nom, prénom du directeur de l'unité de recherche : Pr. Sansonetti, Philippe
Numéro de l'unité de recherche (et établissement de rattachement) : Unité de Pathogénie Microbienne
Moléculaire / Inserm 1202 - Institut Pasteur
Nom, prénom du responsable de l'équipe d'accueil (EAD) : Dr. Marteyn Benoit
Nom, prénom du directeur de thèse : Dr. Marteyn, Benoit
Titre du sujet de thèse proposé :
Oxygen-dependent modulation of neutrophils activation and cell death during Shigella infection
Citer 5 mots clés: neutrophil, oxygen, infection, inflammation, mitochondria
Candidat pressenti :
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OUI
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NON
Contenu scientifique du programme de la thèse
Neutrophils are the most abundant white blood cell population during Shigella infection, which is the
causative agent of the bacillary dysentery (1 million deaths/year worldwide). We previously
demonstrated that hypoxia is induced within Shigella foci of infection: however the impact of this
environment on Shigella virulence or neutrophil physiology remains unknown.
During their lifecycle, neutrophils face low oxygen levels in the bone marrow and in the blood plasma
fraction (98% of the oxygen is bound to red blood cells). Neutrophils face higher oxygen levels when
transmigrating to inflamed or infected organs. Due to their short lifespan in vitro (<8h), neutrophils are
not well studied and remain probably the most mysterious white blood cell population. A better
comprehension of their physiology is urgently needed. Accordingly, we set up and validated an original
neutrophil manipulation strategy under anoxic conditions in order to control their oxygen exposure (time
and dose). We hypothesize that oxygen exposure mediates neutrophil activation and ultimately their cell
death.
Our preliminary results show that upon oxygen exposure mitochondria biogenesis is induced and we
identify a correlation between the mitochondria content and the survival of neutrophils. Mitochondriaassociated cell death seems to be Caspase-independent and involves AIF (Apoptosis Induction Factor).
To which extent oxygen exposure impacts on neutrophil antimicrobial functions is not described.
The aim of the research project is to characterize signalling pathways mediating neutrophil antimicrobial
functions and subsequent cell death upon oxygen exposure in vitro and in vivo. Additionally, the role of
the mitochondria biogenesis in neutrophil activation and cell death will be addressed.
The goals of the PhD project will be to describe and characterize:
1. the biogenesis/degradation of neutrophil mitochondria after oxygen exposure
2. the role of oxygen in neutrophils activation or priming
3. the oxygen-dependent neutrophil cell death signalling pathways
Indiquez les cinq meilleures publications récentes de l’équipe :
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Arena ET, Tinevez JY, Nigro G, Sansonetti PJ, Marteyn BS, The infectious hypoxia: occurrence
and causes during Shigella infection. Microbes Infect. 2016 Nov 21. pii: S1286-4579(16)30171-X
Monceaux, V., Chiche-Lapierre, C., Chaput, C., Witko-Sarsat, V., Prevost, M. C., Taylor, C. T.,
Ungeheuer, M. N., Sansonetti, P. J., Marteyn, BS. Anoxia and glucose supplementation preserve
neutrophil viability and function. Blood. 2016, 128(7): 993-1002.
Anderson, M., Sansonetti, P. J., Marteyn, BS. Shigella diversity and changing landscape: insights
for the twenty-first century. Frontiers in cellular and infection microbiology. 2016, 6:45.
Coic, Y. M., Baleux, F., Poyraz, Ö., Thibeaux, R., Labruyere, E., Chretien, F., Sobhani, I., Lazure,
T., Wypolsz, B., Schneirder, G., Mulard, L., Sansonetti, P. J., Marteyn, BS.. Design of a specific
colonic mucus marker using a human commensal bacterium cell surface domain. J. Biol. Chem..
2012 287(19): 15916-15922.
Marteyn, BS., West, N. P., Browning, D. F., Cole, J.A., Shaw, J. G., Palm, F., Mounier, J.,
Prévost, M. C., Sansonetti P. J., Tang, C. M.. Modulation of Shigella virulence in response to
available oxygen in vivo. Nature. 2010, 465(7296): 355-358.
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