Eukaryotic Intracellular Parasites: Immunity and Chemoresistance

Coordinator : N. Blanchard

Scientific objectives


N. Blanchard

T cell immunity during Toxoplasma gondii and Plasmodium infections

A. Berry

Malaria pathophysiology and chemoresistance

 

 

 

Our research addresses how immunity develops and is modulated by two apicomplexan parasites, Toxoplasma gondii and Plasmodium, which cause toxoplasmosis and malaria respectively. We work also on the epidemiology and mechanisms of drug resistance of malaria parasites.

Malaria affects 200 million people worldwide and kills almost half a million people every year. The biggest toll is on children of sub-Saharan Africa who suffer from deadly complications such as cerebral malaria.

Toxoplasmosis poses serious risk in fetuses if contracted during pregnancy and T. gondii infection may lead to chorioretinitis or encephalitis in immunocompromised individuals. Toxoplasmosis is also a veterinarian issue with a major economical impact for the sheep industry.

These two apicomplexan parasites are unicellular eukaryotic microorganisms residing in a vacuole inside infected cells. The relatively simple asexual cycle and genetic amenability of T. gondii has made it a valuable model parasite for the community interested in apicomplexan parasitic diseases.

Our Projects


AXIS 1: Study antigen presentation and CD8 T cell function during toxoplasmosis

CD8 T cells are key players in protective immunity against T. gondii and Plasmodium. Paradoxically, they can also become pathogenic as is the case during cerebral malaria. Because both T. gondii and Plasmodium dwell within a vacuole segregated from the host cytosol, parasite-derived antigens need to reach beyond the vacuole membrane in order to access the MHC I pathway. This poses major cell biology challenges which are still poorly understood.

The life cycle of T. gondii                                             MHC I presentation pathways for T. gondii antigen processing

Using genetically modified T. gondii and antigen-specific tools (e.g. T cell hybridomas), we have identified critical parameters that control processing of T. gondii antigens in infected cells. Building up on our discovery of a strongly immunogenic protein of T. gondii (GRA6), we demonstrated that the location of the epitope at the C-terminus of the source antigen critically determines processing, immunodominance and protection by GRA6-specific CD8 T cells (Feliu et al, PLoS Path 2013). We found that although ER recruitment via Sec22b is involved in MHC I presentation of luminal antigens (Cebrian et al, Cell 2011), it is not required for GRA6 presentation. For GRA6, topology of membrane insertion determines processing efficiency (Buaillon*, Guerrero* et al, Eur J Immunol 2017).

The host-T. gondii interface comprises the vacuole membrane and an IntraVacuolar Network of tubular membranes (IVN) of mysterious function (Santi-Rocca & Blanchard, Curr Op Microbiology 2017). Using parasite mutants with perturbed GRA6 transport or disrupted IVN, we showed that membrane binding regulates access of T. gondii membrane-bound Ag to the MHC I pathway and that association to the IVN limits presentation and curtails GRA6-specific CD8 responses. Our data indicate that IVN membrane deformations play a role in immune modulation (Lopez et al, Cell Reports 2015).

We are pursuing 2 major objectives:
1- Decipher how vacuole membrane deformations modulate host-parasite exchanges
2- Define the modalities of antigen presentation in the brain during chronic toxoplasmosis, with a focus on MHC I presentation by parasite-infected neurons

‘Mosaic’ of vacuoles containing the Toxoplasma gondii parasite in human fibroblasts

Mouse macrophage invaded by 2 T. gondii parasites

PI: N. Blanchard 
AXIS 2: Decipher how the interplay between dendritic cells and CD4 T cells control protective immunity during blood stage malaria

Cerebral Malaria is a severe complication of malaria, characterized by vascular leakage of brain capillaries, microhemorrhages, edema and coma/death if not treated. Cerebral malaria is associated with sequestration of parasitized Red Blood Cells (pRBC) and leukocytes in microcapillaries.

In experimental rodent models, CD8 T cells are the major effectors of endothelial damage but CD4 Th1 cells also underlie disease development. Yet the parasite antigens presented by MHC class II on dendritic cells (DC) and the roles played by conventional DC in Th polarization are poorly defined. This is particularly relevant since CD4 T cells differentiate into Th subsets, including the B cell-helping T Follicular Helper (TFH), which ultimately determine the balance between antibody-mediated parasite control and immunopathology.

Using a mouse model of cerebral malaria induced by Plasmodium berghei ANKA (Pb ANKA), we have employed proteomics to identify the first MHC II immunopeptidome in malaria (Draheim et al., EMBO Mol Med 2017). We validated the peptides in vivo in infected mice, as well as in long-term protected mice vaccinated with an attenuated parasite. We found that XCR1+ CD8a+ cDC1 are superior to other cells for MHC II presentation of Plasmodium-derived antigens and, using Karma mice that allow depletion of cDC1, we showed that cDC1 promote the differentiation of Th1 cells, which play a pathogenic role in cerebral malaria, and that they inhibit the development of regulatory IL-10+ CD4 Tr1 cells.

We are now trying to globally understand the impact of various DC subsets on Th functionality during malaria. We are also setting out to map the immunopeptidome of P. falciparum in humans.

Furthermore, we are keen to understand why different lines of rodent-adapted Plasmodium elicit different disease outcomes, a mystery that remains poorly understood.

 

 

Mouse red blood cells parasitized with Plasmodium berghei parasites.

 

PI: N. Blanchard
AXIS 3: Monitor the spreading of drug-resistant malaria parasites and analyze the molecular mechanisms of resistance

Regular monitoring of the levels of anti-malarial resistance of P. falciparum is an essential policy to adapt therapy and improve malaria control. In collaboration with Institute for Research and Development, we have assessed the impact of anti-malarial treatments on the emergence and spread of resistant parasites in Cameroon (Ménard et al, Malar J 2012).

Artemisinin-derivatives (ART) are the last still effective anti-malarial class but emergence of resistant P. falciparum raises dramatic public health concerns. In collaboration with F. Benoit-Vical (LCC CNRS, Toulouse), we have demonstrated that F32-ART parasites, a highly ART-resistant, in vitro-selected strain, survive toxic effects of ART through temporary growth arrest, as has been recently reported in malaria isolates from patients in Asia (Witkowski et al, AAC 2010 and AAC 2013). By sequencing the whole genome of F32-ART and its parental line in collaboration with the Pasteur Institutes of Paris and Cambodia, we found mutations which were also present in clinical ART-resistant malaria isolates from South-East Asia. These findings allowed the identification of the first gene strongly associated with ART-resistance (Ariey et al, Nature 2014).

Based on this work, we are addressing 2 specific aims:
1- Monitor the emergence and spread of P. falciparum chemoresistance in Africa and South-East Asia
2- Characterize the mechanisms underlying quiescence of ART-resistant P. falciparum and infer potential strategies to revert this quiescent state

 

A quiescent Plasmodium falciparum parasite in a human erythrocyte following artemisinin treatment

 

 

 

 

OCEAC, Organisation de Coordination et de Coopération pour la lutte contre les grandes Endémies en Afrique Centrale (Yaoundé, Cameroun).

 

 

 

 

Screening children for malaria infection in the Mfou district (Cameroun)

PI: A. Berry 

Other details


Publications

2018

Niare, K; Paloque, L; Menard, S; Tor, P; Ramadani, A P; Augereau, J M; Dara, A; Berry, A; Benoit-Vical, F; Doumbo, O K

Multiple Phenotypic and Genotypic Artemisinin Sensitivity Evaluation of Malian Plasmodium falciparum Isolates Journal Article

Am J Trop Med Hyg, 2018, (Niare, Karamoko Paloque, Lucie Menard, Sandie Tor, Pety Ramadani, Arba P Augereau, Jean-Michel Dara, Antoine Berry, Antoine Benoit-Vical, Francoise Doumbo, Ogobara K Am J Trop Med Hyg. 2018 Feb 12. doi: 10.4269/ajtmh.17-0798.).

Abstract | BibTeX

2017

Bonnart, C; Feuillet, G; Vasseur, V; Cenac, N; Vergnolle, N; Blanchard, N

Protease-Activated Receptor 2 contributes to Toxoplasma gondii-mediated gut inflammation Journal Article

Parasite Immunol, 2017, (Bonnart, Chrystelle Feuillet, Guylene Vasseur, Virginie Cenac, Nicolas Vergnolle, Nathalie Blanchard, Nicolas England Parasite Immunol. 2017 Sep 7. doi: 10.1111/pim.12489.).

Abstract | BibTeX

Buaillon, C; Guerrero, N A; Cebrian, I; Blanie, S; Lopez, J; Bassot, E; Vasseur, V; Santi-Rocca, J; Blanchard, N

MHC I presentation of Toxoplasma gondii immunodominant antigen does not require Sec22b and is regulated by antigen orientation at the vacuole membrane Journal Article

Eur J Immunol, 47 (7), pp. 1160-1170, 2017, (Buaillon, Celia Guerrero, Nestor A Cebrian, Ignacio Blanie, Sophie Lopez, Jodie Bassot, Emilie Vasseur, Virginie Santi-Rocca, Julien Blanchard, Nicolas Germany Eur J Immunol. 2017 Jul;47(7):1160-1170. doi: 10.1002/eji.201646859. Epub 2017 Jun 8.).

Abstract | BibTeX

Draheim, M; Wlodarczyk, M F; Crozat, K; Saliou, J M; Alayi, T D; Tomavo, S; Hassan, A; Salvioni, A; Demarta-Gatsi, C; Sidney, J; Sette, A; Dalod, M; Berry, A; Silvie, O; Blanchard, N

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells Journal Article

EMBO Mol Med, 2017, (Draheim, Marion Wlodarczyk, Myriam F Crozat, Karine Saliou, Jean-Michel Alayi, Tchilabalo Dilezitoko Tomavo, Stanislas Hassan, Ali Salvioni, Anna Demarta-Gatsi, Claudia Sidney, John Sette, Alessandro Dalod, Marc Berry, Antoine Silvie, Olivier Blanchard, Nicolas England EMBO Mol Med. 2017 Sep 21. pii: e201708123. doi: 10.15252/emmm.201708123.).

Abstract | BibTeX

Keita Alassane, S; Nicolau-Travers, M L; Menard, S; Andreoletti, O; Cambus, J P; Gaudre, N; Wlodarczyk, M; Blanchard, N; Berry, A; Abbes, S; Colongo, D; Faye, B; Augereau, J M; Lacroux, C; Iriart, X; Benoit-Vical, F

Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria Journal Article

PLoS One, 12 (7), pp. e0181300, 2017, (Keita Alassane, Sokhna Nicolau-Travers, Marie-Laure Menard, Sandie Andreoletti, Olivier Cambus, Jean-Pierre Gaudre, Noemie Wlodarczyk, Myriam Blanchard, Nicolas Berry, Antoine Abbes, Sarah Colongo, David Faye, Babacar Augereau, Jean-Michel Lacroux, Caroline Iriart, Xavier Benoit-Vical, Francoise PLoS One. 2017 Jul 24;12(7):e0181300. doi: 10.1371/journal.pone.0181300. eCollection 2017.).

Abstract | BibTeX

Lebrun, M; Blanchard, N

Editorial overview: Host-microbe interactions: parasites Journal Article

Curr Opin Microbiol, 40 , pp. viii-xi, 2017, (Lebrun, Maryse Blanchard, Nicolas England Curr Opin Microbiol. 2017 Dec;40:viii-xi. doi: 10.1016/j.mib.2017.11.028.).

BibTeX

Santi-Rocca, J; Blanchard, N

Membrane trafficking and remodeling at the host-parasite interface Journal Article

Curr Opin Microbiol, 40 , pp. 145-151, 2017, (Santi-Rocca, Julien Blanchard, Nicolas England Curr Opin Microbiol. 2017 Dec;40:145-151. doi: 10.1016/j.mib.2017.11.013. Epub 2017 Nov 22.).

Abstract | BibTeX

2016

Cebrian, I; Croce, C; Guerrero, N A; Blanchard, N; Mayorga, L S

Rab22a controls MHC-I intracellular trafficking and antigen cross-presentation by dendritic cells Journal Article

EMBO Rep, 2016, (Cebrian, Ignacio Croce, Cristina Guerrero, Nestor A Blanchard, Nicolas Mayorga, Luis S England EMBO Rep. 2016 Oct 10. pii: e201642358.).

Abstract | BibTeX

Chu, H H; Chan, S W; Gosling, J P; Blanchard, N; Tsitsiklis, A; Lythe, G; Shastri, N; Molina-Paris, C; Robey, E A

Continuous Effector CD8(+) T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population Journal Article

Immunity, 45 (1), pp. 159-71, 2016, (Chu, H Hamlet Chan, Shiao-Wei Gosling, John Paul Blanchard, Nicolas Tsitsiklis, Alexandra Lythe, Grant Shastri, Nilabh Molina-Paris, Carmen Robey, Ellen A Immunity. 2016 Jul 19;45(1):159-71. doi: 10.1016/j.immuni.2016.06.013. Epub 2016 Jul 12.).

Abstract | BibTeX

Latour, C; Wlodarczyk, M F; Jung, G; Gineste, A; Blanchard, N; Ganz, T; Roth, M P; Coppin, H; Kautz, L

Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia Journal Article

Haematologica, 2016, (Latour, Chloe Wlodarczyk, Myriam F Jung, Grace Gineste, Aurelie Blanchard, Nicolas Ganz, Tomas Roth, Marie-Paule Coppin, Helene Kautz, Leon Haematologica. 2016 Sep 22. pii: haematol.2016.150227.).

Abstract | BibTeX

Menard, D; Khim, N; Beghain, J; Adegnika, A A; Shafiul-Alam, M; Amodu, O; Rahim-Awab, G; Barnadas, C; Berry, A; Boum, Y; Bustos, M D; Cao, J; Chen, J H; Collet, L; Cui, L; Thakur, G D; Dieye, A; Djalle, D; Dorkenoo, M A; Eboumbou-Moukoko, C E; Espino, F E; Fandeur, T; Ferreira-da-Cruz, M F; Fola, A A; Fuehrer, H P; Hassan, A M; Herrera, S; Hongvanthong, B; Houze, S; Ibrahim, M L; Jahirul-Karim, M; Jiang, L; Kano, S; Ali-Khan, W; Khanthavong, M; Kremsner, P G; Lacerda, M; Leang, R; Leelawong, M; Li, M; Lin, K; Mazarati, J B; Menard, S; Morlais, I; Muhindo-Mavoko, H; Musset, L; Na-Bangchang, K; Nambozi, M; Niare, K; Noedl, H; Ouedraogo, J B; Pillai, D R; Pradines, B; Quang-Phuc, B; Ramharter, M; Randrianarivelojosia, M; Sattabongkot, J; Sheikh-Omar, A; Silue, K D; Sirima, S B; Sutherland, C; Syafruddin, D; Tahar, R; Tang, L H; Toure, O A; Tshibangu-wa-Tshibangu, P; Vigan-Womas, I; Warsame, M; Wini, L; Zakeri, S; Kim, S; Eam, R; Berne, L; Khean, C; Chy, S; Ken, M; Loch, K; Canier, L; Duru, V; Legrand, E; Barale, J C; Stokes, B; Straimer, J; Witkowski, B; Fidock, D A; Rogier, C; Ringwald, P; Ariey, F; Mercereau-Puijalon, O

A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms Journal Article

N Engl J Med, 374 (25), pp. 2453-64, 2016, (Menard, Didier Khim, Nimol Beghain, Johann Adegnika, Ayola A Shafiul-Alam, Mohammad Amodu, Olukemi Rahim-Awab, Ghulam Barnadas, Celine Berry, Antoine Boum, Yap Bustos, Maria D Cao, Jun Chen, Jun-Hu Collet, Louis Cui, Liwang Thakur, Garib-Das Dieye, Alioune Djalle, Djibrine Dorkenoo, Monique A Eboumbou-Moukoko, Carole E Espino, Fe-Esperanza-Caridad J Fandeur, Thierry Ferreira-da-Cruz, Maria-Fatima Fola, Abebe A Fuehrer, Hans-Peter Hassan, Abdillahi M Herrera, Socrates Hongvanthong, Bouasy Houze, Sandrine Ibrahim, Maman L Jahirul-Karim, Mohammad Jiang, Lubin Kano, Shigeyuki Ali-Khan, Wasif Khanthavong, Maniphone Kremsner, Peter G Lacerda, Marcus Leang, Rithea Leelawong, Mindy Li, Mei Lin, Khin Mazarati, Jean-Baptiste Menard, Sandie Morlais, Isabelle Muhindo-Mavoko, Hypolite Musset, Lise Na-Bangchang, Kesara Nambozi, Michael Niare, Karamoko Noedl, Harald Ouedraogo, Jean-Bosco Pillai, Dylan R Pradines, Bruno Quang-Phuc, Bui Ramharter, Michael Randrianarivelojosia, Milijaona Sattabongkot, Jetsumon Sheikh-Omar, Abdiqani Silue, Kigbafori D Sirima, Sodiomon B Sutherland, Colin Syafruddin, Din Tahar, Rachida Tang, Lin-Hua Toure, Offianan A Tshibangu-wa-Tshibangu, Patrick Vigan-Womas, Ines Warsame, Marian Wini, Lyndes Zakeri, Sedigheh Kim, Saorin Eam, Rotha Berne, Laura Khean, Chanra Chy, Sophy Ken, Malen Loch, Kaknika Canier, Lydie Duru, Valentine Legrand, Eric Barale, Jean-Christophe Stokes, Barbara Straimer, Judith Witkowski, Benoit Fidock, David A Rogier, Christophe Ringwald, Pascal Ariey, Frederic Mercereau-Puijalon, Odile KARMA Consortium AI109023/AI/NIAID NIH HHS/ T32 AI106711/AI/NIAID NIH HHS/ U19AI089702/AI/NIAID NIH HHS/ U19AI089672/AI/NIAID NIH HHS/ R01 AI109023/AI/NIAID NIH HHS/ R01 AI11646601/AI/NIAID NIH HHS/ D43 TW007393/TW/FIC NIH HHS/ U19 AI089672/AI/NIAID NIH HHS/ U19 AI089702/AI/NIAID NIH HHS/ N Engl J Med. 2016 Jun 23;374(25):2453-64. doi: 10.1056/NEJMoa1513137.).

Abstract | BibTeX

Menard, S; Tchoufack, J N; Maffo, C N; Nsango, S E; Iriart, X; Abate, L; Tsapi, M T; Awono-Ambene, P H; Abega Mekongo, F A; Morlais, I; Berry, A

Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles from Cameroonian isolates Journal Article

Malar J, 15 (1), pp. 572, 2016, (Menard, Sandie Tchoufack, Joelle Njila Maffo, Christelle Ngou Nsango, Sandrine E Iriart, Xavier Abate, Luc Tsapi, Majoline Tchioffo Awono-Ambene, Parfait H Abega Mekongo, Francis A Morlais, Isabelle Berry, Antoine England Malar J. 2016 Nov 26;15(1):572.).

Abstract | BibTeX

Sanecka, A; Yoshida, N; Dougan, S K; Jackson, J; Shastri, N; Ploegh, H; Blanchard, N; Frickel, E M

Transnuclear CD8 T cells specific for the immunodominant epitope Gra6 lower acute-phase Toxoplasma gondii burden Journal Article

Immunology, 2016, (Sanecka, Anna Yoshida, Nagisa Dougan, Stephanie K Jackson, John Shastri, Nilabh Ploegh, Hidde Blanchard, Nicolas Frickel, Eva-Maria Immunology. 2016 Jul 5. doi: 10.1111/imm.12643.).

Abstract | BibTeX

Tchioffo, M T; Abate, L; Boissiere, A; Nsango, S E; Gimonneau, G; Berry, A; Oswald, E; Dubois, D; Morlais, I

An epidemiologically successful Escherichia coli sequence type modulates Plasmodium falciparum infection in the mosquito midgut Journal Article

Infect Genet Evol, 43 , pp. 22-30, 2016, (Tchioffo, Majoline T Abate, Luc Boissiere, Anne Nsango, Sandrine E Gimonneau, Geoffrey Berry, Antoine Oswald, Eric Dubois, Damien Morlais, Isabelle Netherlands Infect Genet Evol. 2016 Sep;43:22-30. doi: 10.1016/j.meegid.2016.05.002. Epub 2016 May 3.).

Abstract | BibTeX

2015

Blanchard, N; Dunay, I R; Schluter, D

Persistence of Toxoplasma gondii in the central nervous system: a fine tuned balance between the parasite, the brain and the immune system Journal Article

Parasite Immunol, 2015, (Blanchard, Nicolas Dunay, Ildiko Rita Schluter, Dirk Parasite Immunol. 2015 Jan 9. doi: 10.1111/pim.12173.).

Abstract | BibTeX

Chauvin, P; Menard, S; Iriart, X; Nsango, S E; Tchioffo, M T; Abate, L; Awono-Ambene, P H; Morlais, I; Berry, A

Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaounde, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles Journal Article

J Antimicrob Chemother, 70 (9), pp. 2566-71, 2015, (Chauvin, Pamela Menard, Sandie Iriart, Xavier Nsango, Sandrine E Tchioffo, Majoline T Abate, Luc Awono-Ambene, Parfait H Morlais, Isabelle Berry, Antoine England J Antimicrob Chemother. 2015 Sep;70(9):2566-71. doi: 10.1093/jac/dkv160. Epub 2015 Jun 16.).

Abstract | BibTeX

Joulia, R; Gaudenzio, N; Rodrigues, M; Lopez, J; Blanchard, N; Valitutti, S; Espinosa, E

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence Journal Article

Nat Commun, 6 , pp. 6174, 2015, (Joulia, Regis Gaudenzio, Nicolas Rodrigues, Magda Lopez, Jodie Blanchard, Nicolas Valitutti, Salvatore Espinosa, Eric England Nat Commun. 2015 Jan 28;6:6174. doi: 10.1038/ncomms7174.).

Abstract | BibTeX

Lopez, J; Bittame, A; Massera, C; Vasseur, V; Effantin, G; Valat, A; Buaillon, C; Allart, S; Fox, B A; Rommereim, L M; Bzik, D J; Schoehn, G; Weissenhorn, W; Dubremetz, J F; Gagnon, J; Mercier, C; Cesbron-Delauw, M F; Blanchard, N

Intravacuolar Membranes Regulate CD8 T Cell Recognition of Membrane-Bound Toxoplasma gondii Protective Antigen Journal Article

Cell Rep, 2015, (Lopez, Jodie Bittame, Amina Massera, Celine Vasseur, Virginie Effantin, Gregory Valat, Anne Buaillon, Celia Allart, Sophie Fox, Barbara A Rommereim, Leah M Bzik, David J Schoehn, Guy Weissenhorn, Winfried Dubremetz, Jean-Francois Gagnon, Jean Mercier, Corinne Cesbron-Delauw, Marie-France Blanchard, Nicolas Cell Rep. 2015 Nov 23. pii: S2211-1247(15)01288-7. doi: 10.1016/j.celrep.2015.11.001.).

Abstract | BibTeX

Menard, S; Ben Haddou, T; Ramadani, A P; Ariey, F; Iriart, X; Beghain, J; Bouchier, C; Witkowski, B; Berry, A; Mercereau-Puijalon, O; Benoit-Vical, F

Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure Journal Article

Emerg Infect Dis, 21 (10), pp. 1733-41, 2015, (Menard, Sandie Ben Haddou, Tanila Ramadani, Arba Pramundita Ariey, Frederic Iriart, Xavier Beghain, Johann Bouchier, Christiane Witkowski, Benoit Berry, Antoine Mercereau-Puijalon, Odile Benoit-Vical, Francoise Emerg Infect Dis. 2015 Oct;21(10):1733-41. doi: 10.3201/eid2110.150682.).

Abstract | BibTeX

2013

Ariey, F; Witkowski, B; Amaratunga, C; Beghain, J; Langlois, A C; Khim, N; Kim, S; Duru, V; Bouchier, C; Ma, L; Lim, P; Leang, R; Duong, S; Sreng, S; Suon, S; Chuor, C M; Bout, D M; Menard, S; Rogers, W O; Genton, B; Fandeur, T; Miotto, O; Ringwald, P; Le Bras, J; Berry, A; Barale, J C; Fairhurst, R M; Benoit-Vical, F; Mercereau-Puijalon, O; Menard, D

A molecular marker of artemisinin-resistant Plasmodium falciparum malaria Journal Article

Nature, 2013, (Ariey, Frederic Witkowski, Benoit Amaratunga, Chanaki Beghain, Johann Langlois, Anne-Claire Khim, Nimol Kim, Saorin Duru, Valentine Bouchier, Christiane Ma, Laurence Lim, Pharath Leang, Rithea Duong, Socheat Sreng, Sokunthea Suon, Seila Chuor, Char Meng Bout, Denis Mey Menard, Sandie Rogers, William O Genton, Blaise Fandeur, Thierry Miotto, Olivo Ringwald, Pascal Le Bras, Jacques Berry, Antoine Barale, Jean-Christophe Fairhurst, Rick M Benoit-Vical, Francoise Mercereau-Puijalon, Odile Menard, Didier Nature. 2013 Dec 18. doi: 10.1038/nature12876.).

Abstract | BibTeX

Feliu, V; Vasseur, V; Grover, H S; Chu, H H; Brown, M J; Wang, J; Boyle, J P; Robey, E A; Shastri, N; Blanchard, N

Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite Journal Article

PLoS pathogens, 9 (6), pp. e1003449, 2013, (Feliu, Virginie Vasseur, Virginie Grover, Harshita S Chu, H Hamlet Brown, Mark J Wang, Jeremy Boyle, Jon P Robey, Ellen A Shastri, Nilabh Blanchard, Nicolas PLoS Pathog. 2013 Jun;9(6):e1003449. doi: 10.1371/journal.ppat.1003449. Epub 2013 Jun 20.).

Abstract | BibTeX

Witkowski, B; Khim, N; Chim, P; Kim, S; Ke, S; Kloeung, N; Chy, S; Duong, S; Leang, R; Ringwald, P; Dondorp, A M; Tripura, R; Benoit-Vical, F; Berry, A; Gorgette, O; Ariey, F; Barale, J C; Mercereau-Puijalon, O; Menard, D

Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia Journal Article

Antimicrob Agents Chemother, 57 (2), pp. 914-23, 2013, (Witkowski, Benoit Khim, Nimol Chim, Pheaktra Kim, Saorin Ke, Sopheakvatey Kloeung, Nimol Chy, Sophy Duong, Socheat Leang, Rithea Ringwald, Pascal Dondorp, Arjen M Tripura, Rupam Benoit-Vical, Francoise Berry, Antoine Gorgette, Olivier Ariey, Frederic Barale, Jean-Christophe Mercereau-Puijalon, Odile Menard, Didier Antimicrob Agents Chemother. 2013 Feb;57(2):914-23. doi: 10.1128/AAC.01868-12. Epub 2012 Dec 3.).

Abstract | BibTeX

2012

Menard, S; Morlais, I; Tahar, R; Sayang, C; Mayengue, P I; Iriart, X; Benoit-Vical, F; Lemen, B; Magnaval, J F; Awono-Ambene, P; Basco, L K; Berry, A

Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaounde, Cameroon: implications for the future Journal Article

Malaria journal, 11 , pp. 113, 2012, (Menard, Sandie Morlais, Isabelle Tahar, Rachida Sayang, Collins Mayengue, Pembe Issamou Iriart, Xavier Benoit-Vical, Francoise Lemen, Brigitte Magnaval, Jean-Francois Awono-Ambene, Parfait Basco, Leonardo K Berry, Antoine England Malar J. 2012 Apr 12;11:113.).

Abstract | BibTeX

2011

Cebrian, I; Visentin, G; Blanchard, N; Jouve, M; Bobard, A; Moita, C; Enninga, J; Moita, L F; Amigorena, S; Savina, A

Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells Journal Article

Cell, 147 (6), pp. 1355-68, 2011, (Cebrian, Ignacio Visentin, Geraldine Blanchard, Nicolas Jouve, Mabel Bobard, Alexandre Moita, Catarina Enninga, Jost Moita, Luis F Amigorena, Sebastian Savina, Ariel Cell. 2011 Dec 9;147(6):1355-68.).

Abstract | BibTeX

2008

Blanchard, N; Gonzalez, F; Schaeffer, M; Joncker, N T; Cheng, T; Shastri, A J; Robey, E A; Shastri, N

Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum Journal Article

Nat Immunol, 9 (8), pp. 937-44, 2008, (NLM In-Process Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't DEP - 20080629).

Abstract | BibTeX

Impact on the society

Our field work in Africa will provide valuable information on the spread of Plasmodium isolates that are resistant to artemisinin derivatives as well as to other drugs effective for treating malaria.

These data should allow us to swiftly develop new control strategies in order to limit the burden of these resistant clones. A better understanding of the biology of resistant parasites is also essential to devise new pharmacological strategies.

Our more fundamental work on immunity to Toxoplasma gondii and Plasmodium has the potential to uncover novel pathways / molecules by which intracellular parasites manipulate presentation of their own antigens, modulate immune responses and, more generally, subvert their host. Our studies could also help identify or down-select new vaccine targets.

Alumni

Vincent Cantaloube-Ferrieu (M1 student, 2018)
Julien Santi-Rocca (post-doc 2015-2017)

Myriam Wlodarczyk (post-doc 2012-2017)
Marion Draheim (PhD Student, 2014-2016)
Camille Motbal (M1 student, 2016)
Guillaume Jacob (BTS student, 2016)
Virginie Vasseur (Engineer, 2010-2016)
Marine Le Bouar (M2R student, 2015-2016)
Francesca de Giorgi (Unipharma Graduate Program / Erasmus student, 2016)
Célia Rollin (M2R student 2015-2016)
Célia Buaillon (PhD student 2012-2016)
Jodie Lopez (Graduate student 2012-2015)
Nestor Guerrero (post-doc, 2013-2015)
Giulia Fornabaio (European Unipharma Graduate Program student, 2015)
Noémie Gaudré (Medical student, Master 2R student, 2013-2014)
Valeria Bellini (European Unipharma Graduate Program student, 2012-2013)
Virginie Feliu (Engineer)
Mathilde François (Medical student, Master Student, 2012-2013)
Rose-Anne Lavergne (Intern, Internal Medicine, 2011-2013)
Albano Lima-Perez (Master 2R student, 2012-2013)
Sophie Blanié (post-doc, 2010-2012)
Benjamin Berteloite (Master 1 student, 2011)
Coraline Chéneau (Master 1 student, 2010)

Collaborations
Local

M.-P. Gratacap & B. Payrastre, I2MC INSERM U1048, Toulouse
A. Saoudi, CPTP INSERM U1043, Toulouse
E. Suberbielle, Dunia lab, CPTP INSERM U1043, Toulouse

 

National

F. Benoit-Vical, LCC CNRS UPR 8241, Toulouse
M.-F. Cesbron-Delauw, LAPM CNRS UMR5163, Grenoble
K. Crozat & M. Dalod, CIML, Marseille
I. Morlais & J.-J. Lupez Rubio, MIVEGEC IRD UMR 5290, Montpellier
J.-M. Saliou, P3M proteomics platform, CIIL, Institut Pasteur, Lille
O. Silvie, CIMI-UPMC INSERM U1135, Paris

 

International

P. Awono-Ambene, Yaoundé, Cameroon
I. Cebrian & L. Mayorga, IHEM-CONICET, University of Cuyo, Mendoza, Argentina
D. Ménard, Pasteur Institute, Cambodia
E. Robey, University of California, Berkeley, USA

Institut national de la santé et de la recherche médicale

Institut national de la santé et de la recherche médicale

Centre national de la recherche scientifique

Centre national de la recherche scientifique

Université de Toulouse

Université de Toulouse

Agence nationale de la recherche

Agence nationale de la recherche

Région Occitanie

Région Occitanie

Fondation ARSEP pour la recherche sur la sclérose en plaques

Fondation ARSEP pour la recherche sur la sclérose en plaques

Frontière humaine

Frontière humaine

Aninfimip

Aninfimip

Para Frap

Para Frap

Investissements Avenir

Investissements Avenir

Fondation Bettencourt Schueller

Fondation Bettencourt Schueller