Eukaryotic Pathogens: Inflammation, T cell Immunity and Chemoresistance (EPIIC)

Responsable : N. Blanchard

Scientific objectives


 

 

N. Blanchard

Axis 1.  Pathogenesis and neuroimmune responses during chronic Toxoplasma gondii infection

 

 

 

F. Masson

Axis 2.  Transcriptional regulation of T cell differentiation during neuroinflammatory diseases

 

 

X. Iriart

Axis 3.  Pathophysiology of the adaptive immune response and involvement of inflammation during Pneumocystis infection

 

                                                                                                                       

 A. Berry

Axis 4: Monitor the spreading of drug-resistant malaria parasites and analyze the molecular mechanisms of resistance

 

 

Eukaryotic pathogens affect the lives of millions of individuals throughout the world.  These pathogens include fungi such as Pneumocystis and intracellular parasites such as Toxoplasma gondii and Plasmodium spp.

Pneumocystis pneumonia is an opportunistic fungal disease which induces life-threatening respiratory distress syndrome, and a frequent cause of pneumopathy among immunocompromised patients with a high mortality rate.

Toxoplasmosis is also an opportunistic disease.  It is caused by T. gondii infection and may lead to chorioretinitis or encephalitis in immunocompromised individuals, and fetal abnormalities if contracted during pregnancy.  Even in immunocompetent individuals, latent T. gondii infection has a number of neurological consequences which may have been underestimated so far.

Malaria is the disease caused by Plasmodium infection.  Malaria kills almost half a million people every year, with the biggest toll on children who suffer from deadly complications like cerebral malaria. 

Our research addresses how immunity develops in response to these eukaryotic pathogens.  We are trying to understand the mechanisms by which T cells differentiate and control these pathogens, and how the pathogens may modulate the T cell responses to their benefits.  We also analyze the processes induced by infection that may lead to excessive reactions and immunopathology.  At last, we work on the epidemiology and mechanisms of drug resistance of malaria parasites.

 

 

Our Projects


AXIS 1. Pathogenesis and neuroimmune responses during chronic Toxoplasma gondii infection

 

The Toxoplasma gondii (T. gondii) parasite is a food-borne pathogen that is widespread in the environment.  Its reservoirs are infected animals and contaminated water and soil.  It is estimated that 30% of the population worldwide (up to 50% in France) have been exposed to T. gondii (Fig. 1).

 

Fig. 1. A Toxoplasma tachyzoite within its vacuole. Pseudo-colored artwork of a Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM) stack projected onto one plane.  Credits: J. Santi-Rocca

 

After ingestion of contaminated products, the parasites multiply and reach all tissues of the host including the brain.  Immune reactions are elicited but they are unable to clear the parasite.  T. gondii then establishes latency in cysts that reside in muscular cells and neurons (Fig. 2)

 

 

Fig. 2. A constellation of yellow cysts in a neuronal galaxy.  This image shows a mouse hippocampal neuronal culture infected with red fluorescent Toxoplasma tachyzoites.  Three days post-infection, the culture was labeled with a neuronal (white) and a cyst (green) marker.  Cysts can be visualized as yellow structures scattered within the neuronal dendritic neuronal network.  Credits: M. Belloy & A. Lebourg

 

 

 

In the central nervous system (CNS), T. gondii is under continuous immune surveillance, which avoids parasite reactivation and brain damage.  This surveillance is achieved in large part by parasite-specific CD8+ T cells that detect antigenic fragments from T. gondii presented by MHC I molecules at the surface of infected neurons (Salvioni et al., Cell Reports 2019).  Interestingly, even when efficiently controlled, latent T. gondii infection is associated with multiple neurological disorders, which are thought to be, at least in part, due to neuroinflammation (Laing et al., Trends Immunol 2020). 

 

We are keen to understand the role of the neuron-T cell crosstalk in host immune protection and in the perturbations of neuronal functions induced by the parasite.  Moreover, we have a strong interest in unraveling the consequences of parasite latency outside of the CNS, i.e. on the peripheral (enteric) nervous system.  

 

Our previous work has allowed us to design unique models to study the neuroimmune crosstalk (Fig. 3).  

 

 

Fig. 3. Three in vivo models to study Toxoplasma infection.  Depending on the immunodominant antigen expressed by the parasites (GRA6-OVA vs. SAG1-OVA) and the timing of administration of the pyrimethamine anti-parasite drug, the outcome of infection varies from clearance to latency to encephalitis, thereby recapitulating the different contexts of human infection.

 

These models recapitulate 3 situations that are observed in humans: latency (most frequent), encephalitis (may occur in case of acquired immune deficiency), clearance (may occur in case of prompt anti-parasitic drug treatment).  We are now studying:

1- how the neuroimmune crosstalk controls behavioral changes and neurodegeneration during T. gondii infection

Project leader : M. Belloy (PhD student)

Collaboration : Dr E. Suberbielle and Dr N. Fazilleau, Infinity, Toulouse

2- how the neuroimmune crosstalk controls T. gondii-induced changes in intestinal homestasis and visceral sensitivity

Project leader : A. Audibert (PhD student)

Collaboration : Dr C. Bonnart, Dr G. Dietrich and Dr N. Cenac, IRSD, Toulouse

3- the function(s) and mechanisms of differentiation/maintenance of brain-resident memory CD8+ T cells during chronic T. gondii infection

Project leaders : R. Porte (postdoc), M. Belloy (PhD student), A. Audibert (PhD student)

Collaboration : Dr K. van Gisbergen, Sanquin Institute, The Netherlands ; Dr F. Masson, Infinity

4- how T. gondii cysts evade CD8 T cell recognition to establish latency

Project leader : Parafrap PhD student to be recruited

Collaboration : Dr M.-A. Hakimi, IAB, Grenoble

 

Given that T. gondii cysts cannot be eradicated pharmacologically, CD8+ T cells represent valuable cellular targets to harness in order to eliminate the parasite from latently infected hosts.

Axis 2. Transcriptional regulation of T cell differentiation during neuroinflammatory diseases

 

We are interested by the molecular mechanisms that regulate the functional specialization of T lymphocytes during neuroinflammatory diseases caused by a pathogen infection (in particular the infection by the intracellular parasite Toxoplasma gondii) or during CNS auto-immunity (multiple sclerosis).

 

Specifically, we are investigating the mechanisms by which key transcriptional regulators control the differentiation of T cells into effector and memory cells (Fig. 1), as well their roles in these various pathophysiological contexts, which may be either protective or pathogenic.

 

Fig. 1. Model of peripheral CD8+ T cell differentiation during a pathogen infection.  Credits F. Masson

 

 

We are using in vivo experimental models of neuroinflammation (infection by T. gondii, experimental autoimmune encephalitis (EAE)) associated with state-of-the-art molecular tools including inducible lentiviral and retroviral vectors allowing genetic alteration of T cells in an inducible manner.

 

Our projects aim at identifying new therapeutic strategies that are more targeted and efficacious against neuroinflammatory diseases through the functional reprogramming of T lymphocytes.

Axis 3. Pathophysiology of the adaptive immune response and involvement of inflammation during Pneumocystis infection

 

Pneumocystis pneumonia (PCP) is an opportunistic fungal disease which induces potentially life-threatening respiratory distress syndrome.  While immunocompetent hosts spontaneously eliminate the fungus (Fig. 1) without any symptoms, PCP is a frequent cause of pneumopathy among immunocompromised patients, with a mortality estimated at ~20%.  Yet, PCP and the associated immune responses are understudied.

 

 

Fig. 1.  Pneumocystosis in an in vivo experimental model infected with Pneumocystis murina: Pneumocystis cysts stained with Gomori Grocott (red arrows)

 

 

 

 

Our group addresses 2 specific aims on the topic of Pneumocystis infection:

  1. A better understanding of the pathophysiological mechanisms of PCP, particularly adaptive immunity and host inflammatory response

PCP pathophysiology remains poorly understood.  However, it is generally accepted that the lung lesions observed during the disease are largely due to an unsuitable host immune response (Fig. 2).  We previously identified pro-inflammatory and pro-resolving lipid mediators which seem to be implicated in the pathophysiology of the disease both in PCP patients and in in vivo experimental models of Pneumocystis infection.  

 

Fig. 2. Pneumocystosis in an in vivo experimental model infected with Pneumocystis murina: Alveolar exudates after staining with Hematoxylin-Eosin (yellow arrows)

 

 

 

As the lymphocyte response is crucial in the disease development, we are investigating the implication of the different CD4+ T lymphocyte subsets in the pathophysiology of Pneumocystis infection and their potential as key effector cells to control PCP pathology.

 

  1. The definition of biomarkers predictive of the risk or the outcome of PCP

Identifying biological markers predictive of a high PCP risk or outcome is essential for the clinical management of immunocompromised patients.  Thanks to clinical studies, we have already identified lymphocyte subsets and pro-inflammatory lipid mediators associated with unfavourable evolution of PCP.

Prophylactic treatments are effective in preventing the development of PCP in immunocompromised patients.  Nevertheless, there is no good biomarker of PCP risk for the HIV-negative population.  Using in vivo experimental models of PCP, we identified lymphocyte subsets which seem to be associated with Pneumocystis elimination in immunocompetent subjects without notable inflammation.  

Using clinical studies and in vivo experimental models of PCP, our project aims at evaluating the potential interest of these populations as biomarkers of PCP risk, particularly in immunocompromised HIV-negative patients.

Axis 4: 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 ensure effective malaria control.  In collaboration with the Institute for Research and Development and the Pasteur Center of Cameroon, we assess the impact of anti-malarial treatments on the emergence and spread of resistant parasites in Cameroon (Ménard et al, Malar J 2012 and Malar J. 2016; Chauvin et al, J Antimicrob Chemother 2015).

 

Artemisinin-derivatives (ART) are the last still effective anti-malarial class but emergence of resistant P. falciparum first identified in Southeast Asia and recently in Africa, is a dramatic public health concern.  In collaboration with F. Benoit-Vical (LCC CNRS, Toulouse), then with the Pasteur Institutes of Paris and Cambodia, we have demonstrated that a strain highly resistant to ART in vitro, survives toxic effects of ART through temporary growth arrest (quiescence), as has been reported in malaria isolates from patients in Asia (Witkowski et al, AAC 2010 and AAC 2013).  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.
    2. Characterize the mechanisms underlying quiescence of ART-resistant P. falciparum.

 

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)

Other details


Publications

2020

Cerutti, A; Blanchard, N; Besteiro, S

The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis Journal Article

Pathogens, 9 (3), 2020, (doi: 10.3390/pathogens9030234.).

Abstract | BibTeX

Charpentier, E; Benichou, E; Pages, A; Chauvin, P; Fillaux, J; Valentin, A; Guegan, H; Guemas, E; Salabert, A S; Armengol, C; Menard, S; Cassaing, S; Berry, A; Iriart, X

Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria Journal Article

Clin Microbiol Infect, 26 (1), pp. 115-121, 2020, (doi: 10.1016/j.cmi.2019.05.010. Epub 2019 May 31.).

Abstract | BibTeX

Hassan, A; Wlodarczyk, M F; Benamar, M; Bassot, E; Salvioni, A; Kassem, S; Berry, A; Saoudi, A; Blanchard, N

A Virus Hosted in Malaria-Infected Blood Protects against T Cell-Mediated Inflammatory Diseases by Impairing DC Function in a Type I IFN-Dependent Manner Journal Article

mBio, 11 (2), 2020, (doi: 10.1128/mBio.03394-19.).

Abstract | BibTeX

Iriart, X; Menard, S; Chauvin, P; Mohamed, H S; Charpentier, E; Mohamed, M A; Berry, A; Aboubaker, M H

Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case Journal Article

Emerg Microbes Infect, 9 (1), pp. 1984-1987, 2020, (doi: 10.1080/22221751.2020.1815590.).

Abstract | BibTeX

Kaminski, H; Belliere, J; Burguet, L; Del Bello, A; Taton, B; Poirot-Mazeres, S; Accoceberry, I; Delhaes, L; Visentin, J; Gregori, M; Iriart, X; Charpentier, E; Couzi, L; Kamar, N; Merville, P

Identification of predictive markers and outcomes of late-onset Pneumocystis jirovecii pneumonia in kidney transplant recipients Journal Article

Clin Infect Dis, 2020, (doi: 10.1093/cid/ciaa1611.).

Abstract | BibTeX

Laing, C; Blanchard, N; McConkey, G A

Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes Journal Article

Trends Immunol, 41 (12), pp. 1072-1082, 2020, (doi: 10.1016/j.it.2020.10.001. Epub 2020 Nov 16.).

Abstract | BibTeX

2019

Salvioni, A; Belloy, M; Lebourg, A; Bassot, E; Cantaloube-Ferrieu, V; Vasseur, V; Blanie, S; Liblau, R S; Suberbielle, E; Robey, E A; Blanchard, N

Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons Journal Article

Cell Rep, 27 (11), pp. 3254-3268 e8, 2019, (Jun 11;27(11):3254-3268.e8. doi: 10.1016/j.celrep.2019.05.051.).

Abstract | BibTeX

Charpentier, E; Benichou, E; Pages, A; Chauvin, P; Fillaux, J; Valentin, A; Guegan, H; Guemas, E; Salabert, A S; Armengol, C; Menard, S; Cassaing, S; Berry, A; Iriart, X

Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria Journal Article

Clin Microbiol Infect, 2019, (May 31. pii: S1198-743X(19)30225-3. doi: 10.1016/j.cmi.2019.05.010.).

Abstract | BibTeX

Poncet, A F; Blanchard, N; Marion, S

Toxoplasma and Dendritic Cells: An Intimate Relationship That Deserves Further Scrutiny Journal Article

Trends Parasitol, 2019, (Sep 3. pii: S1471-4922(19)30210-7. doi: 10.1016/j.pt.2019.08.001.).

Abstract | BibTeX

Guegan, H; Fillaux, J; Charpentier, E; Robert-Gangneux, F; Chauvin, P; Guemas, E; Boissier, J; Valentin, A; Cassaing, S; Gangneux, J P; Berry, A; Iriart, X

Real-time PCR for diagnosis of imported schistosomiasis Journal Article

PLoS Negl Trop Dis, 13 (9), pp. e0007711, 2019.

Abstract | BibTeX

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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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, (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 fundamental work on immunity to Toxoplasma gondii and Plasmodium has the potential to uncover novel pathways and/or molecules by which intracellular parasites manipulate presentation of their own antigens, modulate immune responses and, more generally, subvert their host.

Our studies could help identify or down-select new vaccine targets.  They may also suggest approaches to use CD8 T cells in order to eradicate T. gondii cysts, against which there is currently no effective pharmacological treatment.

Collaborations
Local

Dr Chrystelle Bonnart, N. Vergnolle’s team, Institute for Research on Digestive Health, Toulouse

Drs Gilles Dietrich & Nicolas Cenac, Institute for Research on Digestive Health, Toulouse

Dr Nicolas Fazilleau, Infinity

Drs Roland Liblau & Abdelhadi Saoudi, Infinity

Dr Elsa Suberbielle, D. Dunia’s team, Infinity

National

Dr Antoine Claessens, LPHI, Montpellier

Dr Sylvie Garcia, A. Sherf’s team, Pasteur Institute, Paris

Dr Mohamed-Ali Hakimi, IAB, Grenoble

Dr Sabrina Marion, CIIL / Pasteur Institute, Lille

Dr Isabelle Morlais, MIVEGEC, Montpellier

International

Pr Parfait Awono-Ambene, Yaoundé, Cameroon

Drs Ignacio Cebrian & Luis Mayorga, IHEM-CONICET, University of Cuyo, Mendoza, Argentina

Dr Klaas van Gisbergen, Sanquin Institute, The Netherlands

Pr Ellen Robey, University of California, Berkeley, USA

Alumni

Eléna Charpentier, Pharm.D. (PhD student 2017-2020)

Aurore Lebourg (Engineer 2018-2020)

Mélissa Mairet-Khedim (PhD student 2016-2020)

Ali Hassan (PhD student 2016-2019)

Anna Salvioni (PhD student 2016-2019)

Nian-Zhang Zhang (Visiting Scholar from Lanzhou Veterinary Research Institute, China, 2017-2019)

Julien Santi-Rocca (post-doc 2015-2017)

Myriam Wlodarczyk (post-doc 2012-2017)

Marion Draheim (PhD Student, 2014-2016)

Virginie Vasseur (Engineer, 2010-2016)

Francesca de Giorgi (Unipharma Graduate Program / Erasmus student, 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).

Valeria Bellini (European Unipharma Graduate Program student, 2012-2013).

Virginie Feliu (Engineer).

Rose-Anne Lavergne, MD (Interne 2011-2013).

Sophie Blanié (Post-doc, 2010-2012).

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