Liblau, Roland S.; Gonzalez-Dunia, Daniel; Wiendl, Heinz; Zipp, Frauke Neurons as targets for T cells in the nervous system Article de journal Dans: Trends in Neurosciences, vol. 36, no. 6, p. 315–324, 2013, ISSN: 0166-2236. @article{Liblau2013,
title = {Neurons as targets for T cells in the nervous system},
author = {Roland S. Liblau and Daniel Gonzalez-Dunia and Heinz Wiendl and Frauke Zipp},
doi = {10.1016/j.tins.2013.01.008},
issn = {0166-2236},
year = {2013},
date = {2013-06-00},
urldate = {2013-06-00},
journal = {Trends in Neurosciences},
volume = {36},
number = {6},
pages = {315--324},
publisher = {Elsevier BV},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Suberbielle, Elsa; Sanchez, Pascal E; Kravitz, Alexxai V; Wang, Xin; Ho, Kaitlyn; Eilertson, Kirsten; Devidze, Nino; Kreitzer, Anatol C; Mucke, Lennart Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β Article de journal Dans: Nat Neurosci, vol. 16, no. 5, p. 613–621, 2013, ISSN: 1546-1726. @article{Suberbielle2013,
title = {Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β},
author = {Elsa Suberbielle and Pascal E Sanchez and Alexxai V Kravitz and Xin Wang and Kaitlyn Ho and Kirsten Eilertson and Nino Devidze and Anatol C Kreitzer and Lennart Mucke},
doi = {10.1038/nn.3356},
issn = {1546-1726},
year = {2013},
date = {2013-05-00},
urldate = {2013-05-00},
journal = {Nat Neurosci},
volume = {16},
number = {5},
pages = {613--621},
publisher = {Springer Science and Business Media LLC},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Pellerin, Laurence; Henry, Julie; Hsu, Chiung-Yueh; Balica, Stéfana; Jean-Decoster, Catherine; Méchin, Marie-Claire; Hansmann, Britta; Rodriguez, Elke; Weindinger, Stefan; Schmitt, Anne-Marie; Serre, Guy; Paul, Carle; Simon, Michel Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. Article de journal Dans: The Journal of allergy and clinical immunology, vol. 131, no. 4, p. 1094–1102, 2013, ISSN: 1097-6825 (Electronic). @article{Pellerin2013,
title = {Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin.},
author = {Pellerin, Laurence and Henry, Julie and Hsu, Chiung-Yueh and Balica, Stéfana and Jean-Decoster, Catherine and Méchin, Marie-Claire and Hansmann, Britta and Rodriguez, Elke and Weindinger, Stefan and Schmitt, Anne-Marie and Serre, Guy and Paul, Carle and Simon, Michel},
doi = {10.1016/j.jaci.2012.12.1566},
issn = {1097-6825 (Electronic)},
year = {2013},
date = {2013-04-01},
journal = {The Journal of allergy and clinical immunology},
volume = {131},
number = {4},
pages = {1094--1102},
abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG). OBJECTIVES: We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD. METHODS: An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25. RESULTS: Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels. CONCLUSION: The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG). OBJECTIVES: We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD. METHODS: An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25. RESULTS: Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels. CONCLUSION: The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction. |
Salles, J. P.; Laurencin-Dalicieux, S.; Conte-Auriol, F.; Briand-Mesange, F.; Gennero, I. Bone defects in LPA receptor genetically modified mice Article de journal Dans: Biochim Biophys Acta, vol. 1831, no. 1, p. 93-8, 2013, ISSN: 0006-3002 (Print)
0006-3002 (Linking). @article{RN37,
title = {Bone defects in LPA receptor genetically modified mice},
author = {Salles, J. P. and Laurencin-Dalicieux, S. and Conte-Auriol, F. and Briand-Mesange, F. and Gennero, I.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22867754},
doi = {10.1016/j.bbalip.2012.07.018},
issn = {0006-3002 (Print)
0006-3002 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Biochim Biophys Acta},
volume = {1831},
number = {1},
pages = {93-8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Davignon, J. L.; Hayder, M.; Baron, M.; Boyer, J. F.; Constantin, A.; Apparailly, F.; Poupot, R.; Cantagrel, A. Targeting monocytes/macrophages in the treatment of rheumatoid arthritis Article de journal Dans: Rheumatology (Oxford), vol. 52, no. 4, p. 590-8, 2013, ISSN: 1462-0332 (Electronic)
1462-0324 (Linking). @article{RN15b,
title = {Targeting monocytes/macrophages in the treatment of rheumatoid arthritis},
author = {Davignon, J. L. and Hayder, M. and Baron, M. and Boyer, J. F. and Constantin, A. and Apparailly, F. and Poupot, R. and Cantagrel, A.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23204551},
doi = {10.1093/rheumatology/kes304},
issn = {1462-0332 (Electronic)
1462-0324 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Rheumatology (Oxford)},
volume = {52},
number = {4},
pages = {590-8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Fruchon, S.; Caminade, A. M.; Abadie, C.; Davignon, J. L.; Combette, J. M.; Turrin, C. O.; Poupot, R. An azabisphosphonate-capped poly(phosphorhydrazone) dendrimer for the treatment of endotoxin-induced uveitis Article de journal Dans: Molecules, vol. 18, no. 8, p. 9305-16, 2013, ISSN: 1420-3049 (Electronic)
1420-3049 (Linking). @article{RN20,
title = {An azabisphosphonate-capped poly(phosphorhydrazone) dendrimer for the treatment of endotoxin-induced uveitis},
author = {Fruchon, S. and Caminade, A. M. and Abadie, C. and Davignon, J. L. and Combette, J. M. and Turrin, C. O. and Poupot, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23921793},
doi = {10.3390/molecules18089305},
issn = {1420-3049 (Electronic)
1420-3049 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Molecules},
volume = {18},
number = {8},
pages = {9305-16},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Guerder, S.; Joncker, N.; Mahiddine, K.; Serre, L. Dendritic cells in tolerance and autoimmune diabetes Article de journal Dans: Curr Opin Immunol, vol. 25, no. 6, p. 670-5, 2013, ISSN: 1879-0372 (Electronic)
0952-7915 (Linking). @article{RN7b,
title = {Dendritic cells in tolerance and autoimmune diabetes},
author = {Guerder, S. and Joncker, N. and Mahiddine, K. and Serre, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24168964},
doi = {10.1016/j.coi.2013.10.004},
issn = {1879-0372 (Electronic)
0952-7915 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Curr Opin Immunol},
volume = {25},
number = {6},
pages = {670-5},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Pasquet, L.; Douet, J. Y.; Sparwasser, T.; Romagnoli, P.; van Meerwijk, J. P. M. Long-term prevention of chronic allograft rejection by regulatory T-cell immunotherapy involves host Foxp3-expressing T cells Article de journal Dans: Blood, vol. 121, no. 21, p. 4303-10, 2013, ISSN: 1528-0020 (Electronic)
0006-4971 (Linking). @article{RN173,
title = {Long-term prevention of chronic allograft rejection by regulatory T-cell immunotherapy involves host Foxp3-expressing T cells},
author = {Pasquet, L. and Douet, J. Y. and Sparwasser, T. and Romagnoli, P. and van Meerwijk, J. P. M.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23580663},
doi = {10.1182/blood-2012-08-452037},
issn = {1528-0020 (Electronic)
0006-4971 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Blood},
volume = {121},
number = {21},
pages = {4303-10},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Tellier, J.; Andrianjaka, A.; Vicente, R.; Thiault, N.; Enault, G.; Garchon, H. J.; van Meerwijk, J. P. M.; Romagnoli, P. Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility Article de journal Dans: Eur J Immunol, vol. 43, no. 5, p. 1356-62, 2013, ISSN: 1521-4141 (Electronic)
0014-2980 (Linking). @article{RN174,
title = {Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility},
author = {Tellier, J. and Andrianjaka, A. and Vicente, R. and Thiault, N. and Enault, G. and Garchon, H. J. and van Meerwijk, J. P. M. and Romagnoli, P.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23400928},
doi = {10.1002/eji.201243142},
issn = {1521-4141 (Electronic)
0014-2980 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Eur J Immunol},
volume = {43},
number = {5},
pages = {1356-62},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Pelletier, L.; Savignac, M. Ca(2+) signaling in T-cell subsets with a focus on the role of cav1 channels: possible implications in therapeutics Article de journal Dans: Front Immunol, vol. 4, p. 150, 2013, ISSN: 1664-3224 (Print)
1664-3224 (Linking). @article{RN15,
title = {Ca(2+) signaling in T-cell subsets with a focus on the role of cav1 channels: possible implications in therapeutics},
author = {Pelletier, L. and Savignac, M.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23801988},
doi = {10.3389/fimmu.2013.00150},
issn = {1664-3224 (Print)
1664-3224 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Front Immunol},
volume = {4},
pages = {150},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Robert, V.; Triffaux, E.; Savignac, M.; Pelletier, L. Singularities of calcium signaling in effector T-lymphocytes Article de journal Dans: Biochim Biophys Acta, vol. 1833, no. 7, p. 1595-602, 2013, ISSN: 0006-3002 (Print)
0006-3002 (Linking). @article{RN16b,
title = {Singularities of calcium signaling in effector T-lymphocytes},
author = {Robert, V. and Triffaux, E. and Savignac, M. and Pelletier, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23266355},
doi = {10.1016/j.bbamcr.2012.12.001},
issn = {0006-3002 (Print)
0006-3002 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Biochim Biophys Acta},
volume = {1833},
number = {7},
pages = {1595-602},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Seillet, C.; Rouquie, N.; Foulon, E.; Douin-Echinard, V.; Krust, A.; Chambon, P.; Arnal, J. F.; Guery, J. C.; Laffont, S. Estradiol Promotes Functional Responses in Inflammatory and Steady-State Dendritic Cells through Differential Requirement for Activation Function-1 of Estrogen Receptor alpha Article de journal Dans: J. Immunol., vol. 190, no. 11, p. 5459-70, 2013, ISSN: 1550-6606 (Electronic)
0022-1767 (Linking). @article{RN10b,
title = {Estradiol Promotes Functional Responses in Inflammatory and Steady-State Dendritic Cells through Differential Requirement for Activation Function-1 of Estrogen Receptor alpha},
author = {Seillet, C. and Rouquie, N. and Foulon, E. and Douin-Echinard, V. and Krust, A. and Chambon, P. and Arnal, J. F. and Guery, J. C. and Laffont, S.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23626011
http://www.jimmunol.org/content/190/11/5459.full.pdf},
doi = {10.4049/jimmunol.1203312},
issn = {1550-6606 (Electronic)
0022-1767 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {J. Immunol.},
volume = {190},
number = {11},
pages = {5459-70},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
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 Article de journal Dans: 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.). @article{b,
title = {A molecular marker of artemisinin-resistant Plasmodium falciparum malaria},
author = {Ariey, F. and Witkowski, B. and Amaratunga, C. and Beghain, J. and Langlois, A. C. and Khim, N. and Kim, S. and Duru, V. and Bouchier, C. and Ma, L. and Lim, P. and Leang, R. and Duong, S. and Sreng, S. and Suon, S. and Chuor, C. M. and Bout, D. M. and Menard, S. and Rogers, W. O. and Genton, B. and Fandeur, T. and Miotto, O. and Ringwald, P. and Le Bras, J. and Berry, A. and Barale, J. C. and Fairhurst, R. M. and Benoit-Vical, F. and Mercereau-Puijalon, O. and Menard, D.},
year = {2013},
date = {2013-01-01},
journal = {Nature},
abstract = {Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.},
note = {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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread. |
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 Article de journal Dans: PLoS pathogens, vol. 9, no. 6, p. 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.). @article{b,
title = {Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite},
author = {Feliu, V. and Vasseur, V. and Grover, H. S. and Chu, H. H. and Brown, M. J. and Wang, J. and Boyle, J. P. and Robey, E. A. and Shastri, N. and Blanchard, N.},
year = {2013},
date = {2013-01-01},
journal = {PLoS pathogens},
volume = {9},
number = {6},
pages = {e1003449},
abstract = {CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood. Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells.},
note = {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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood. Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells. |
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 Article de journal Dans: Antimicrob Agents Chemother, vol. 57, no. 2, p. 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.). @article{b,
title = {Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia},
author = {Witkowski, B. and Khim, N. and Chim, P. and Kim, S. and Ke, S. and Kloeung, N. and Chy, S. and Duong, S. and Leang, R. and Ringwald, P. and Dondorp, A. M. and Tripura, R. and Benoit-Vical, F. and Berry, A. and Gorgette, O. and Ariey, F. and Barale, J. C. and Mercereau-Puijalon, O. and Menard, D.},
year = {2013},
date = {2013-01-01},
journal = {Antimicrob Agents Chemother},
volume = {57},
number = {2},
pages = {914-23},
abstract = {The declining efficacy of artemisinin derivatives against Plasmodium falciparum in western Cambodia is a major concern. The knowledge gap in the understanding of the mechanisms involved hampers designing monitoring tools. Here, we culture-adapted 20 isolates from Pailin and Ratanakiri (areas of artemisinin resistance and susceptibility in western and eastern Cambodia, respectively) and studied their in vitro response to dihydroartemisinin. No significant difference between the two sets of isolates was observed in the classical isotopic test. However, a 6-h pulse exposure to 700 nM dihydroartemisinin (ring-stage survival assay -RSA]) revealed a clear-cut geographic dichotomy. The survival rate of exposed ring-stage parasites (ring stages) was 17-fold higher in isolates from Pailin (median, 13.5%) than in those from Ratanakiri (median, 0.8%), while exposed mature stages were equally and highly susceptible (0.6% and 0.7%, respectively). Ring stages survived drug exposure by cell cycle arrest and resumed growth upon drug withdrawal. The reduced susceptibility to artemisinin in Pailin appears to be associated with an altered in vitro phenotype of ring stages from Pailin in the RSA.},
note = {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.},
keywords = {},
pubstate = {published},
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The declining efficacy of artemisinin derivatives against Plasmodium falciparum in western Cambodia is a major concern. The knowledge gap in the understanding of the mechanisms involved hampers designing monitoring tools. Here, we culture-adapted 20 isolates from Pailin and Ratanakiri (areas of artemisinin resistance and susceptibility in western and eastern Cambodia, respectively) and studied their in vitro response to dihydroartemisinin. No significant difference between the two sets of isolates was observed in the classical isotopic test. However, a 6-h pulse exposure to 700 nM dihydroartemisinin (ring-stage survival assay -RSA]) revealed a clear-cut geographic dichotomy. The survival rate of exposed ring-stage parasites (ring stages) was 17-fold higher in isolates from Pailin (median, 13.5%) than in those from Ratanakiri (median, 0.8%), while exposed mature stages were equally and highly susceptible (0.6% and 0.7%, respectively). Ring stages survived drug exposure by cell cycle arrest and resumed growth upon drug withdrawal. The reduced susceptibility to artemisinin in Pailin appears to be associated with an altered in vitro phenotype of ring stages from Pailin in the RSA. |
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 Article de journal Dans: Nature, 2013, (Dec 18. doi: 10.1038/nature12876.). @article{,
title = {A molecular marker of artemisinin-resistant Plasmodium falciparum malaria},
author = {Ariey, F. and Witkowski, B. and Amaratunga, C. and Beghain, J. and Langlois, A. C. and Khim, N. and Kim, S. and Duru, V. and Bouchier, C. and Ma, L. and Lim, P. and Leang, R. and Duong, S. and Sreng, S. and Suon, S. and Chuor, C. M. and Bout, D. M. and Menard, S. and Rogers, W. O. and Genton, B. and Fandeur, T. and Miotto, O. and Ringwald, P. and Le Bras, J. and Berry, A. and Barale, J. C. and Fairhurst, R. M. and Benoit-Vical, F. and Mercereau-Puijalon, O. and Menard, D.},
year = {2013},
date = {2013-01-01},
journal = {Nature},
abstract = {Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.},
note = {Dec 18. doi: 10.1038/nature12876.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread. |
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 Article de journal Dans: PLoS pathogens, vol. 9, no. 6, p. e1003449, 2013, (Jun;9(6):e1003449. doi: 10.1371/journal.ppat.1003449. Epub 2013 Jun 20.). @article{b,
title = {Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite},
author = {Feliu, V. and Vasseur, V. and Grover, H. S. and Chu, H. H. and Brown, M. J. and Wang, J. and Boyle, J. P. and Robey, E. A. and Shastri, N. and Blanchard, N.},
year = {2013},
date = {2013-01-01},
journal = {PLoS pathogens},
volume = {9},
number = {6},
pages = {e1003449},
abstract = {CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood. Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells.},
note = {Jun;9(6):e1003449. doi: 10.1371/journal.ppat.1003449. Epub 2013 Jun 20.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
CD8 T cells protect the host from disease caused by intracellular pathogens, such as the Toxoplasma gondii (T. gondii) protozoan parasite. Despite the complexity of the T. gondii proteome, CD8 T cell responses are restricted to only a small number of peptide epitopes derived from a limited set of antigenic precursors. This phenomenon is known as immunodominance and is key to effective vaccine design. However, the mechanisms that determine the immunogenicity and immunodominance hierarchy of parasite antigens are not well understood. Here, using genetically modified parasites, we show that parasite burden is controlled by the immunodominant GRA6-specific CD8 T cell response but not by responses to the subdominant GRA4- and ROP7-derived epitopes. Remarkably, optimal processing and immunodominance were determined by the location of the peptide epitope at the C-terminus of the GRA6 antigenic precursor. In contrast, immunodominance could not be explained by the peptide affinity for the MHC I molecule or the frequency of T cell precursors in the naive animals. Our results reveal the molecular requirements for optimal presentation of an intracellular parasite antigen and for eliciting protective CD8 T cells. |
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 Article de journal Dans: Antimicrob Agents Chemother, vol. 57, no. 2, p. 914-23, 2013, (Feb;57(2):914-23. doi: 10.1128/AAC.01868-12. Epub 2012 Dec 3.). @article{b,
title = {Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia},
author = {Witkowski, B. and Khim, N. and Chim, P. and Kim, S. and Ke, S. and Kloeung, N. and Chy, S. and Duong, S. and Leang, R. and Ringwald, P. and Dondorp, A. M. and Tripura, R. and Benoit-Vical, F. and Berry, A. and Gorgette, O. and Ariey, F. and Barale, J. C. and Mercereau-Puijalon, O. and Menard, D.},
year = {2013},
date = {2013-01-01},
journal = {Antimicrob Agents Chemother},
volume = {57},
number = {2},
pages = {914-23},
abstract = {The declining efficacy of artemisinin derivatives against Plasmodium falciparum in western Cambodia is a major concern. The knowledge gap in the understanding of the mechanisms involved hampers designing monitoring tools. Here, we culture-adapted 20 isolates from Pailin and Ratanakiri (areas of artemisinin resistance and susceptibility in western and eastern Cambodia, respectively) and studied their in vitro response to dihydroartemisinin. No significant difference between the two sets of isolates was observed in the classical isotopic test. However, a 6-h pulse exposure to 700 nM dihydroartemisinin (ring-stage survival assay -RSA]) revealed a clear-cut geographic dichotomy. The survival rate of exposed ring-stage parasites (ring stages) was 17-fold higher in isolates from Pailin (median, 13.5%) than in those from Ratanakiri (median, 0.8%), while exposed mature stages were equally and highly susceptible (0.6% and 0.7%, respectively). Ring stages survived drug exposure by cell cycle arrest and resumed growth upon drug withdrawal. The reduced susceptibility to artemisinin in Pailin appears to be associated with an altered in vitro phenotype of ring stages from Pailin in the RSA.},
note = {Feb;57(2):914-23. doi: 10.1128/AAC.01868-12. Epub 2012 Dec 3.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The declining efficacy of artemisinin derivatives against Plasmodium falciparum in western Cambodia is a major concern. The knowledge gap in the understanding of the mechanisms involved hampers designing monitoring tools. Here, we culture-adapted 20 isolates from Pailin and Ratanakiri (areas of artemisinin resistance and susceptibility in western and eastern Cambodia, respectively) and studied their in vitro response to dihydroartemisinin. No significant difference between the two sets of isolates was observed in the classical isotopic test. However, a 6-h pulse exposure to 700 nM dihydroartemisinin (ring-stage survival assay -RSA]) revealed a clear-cut geographic dichotomy. The survival rate of exposed ring-stage parasites (ring stages) was 17-fold higher in isolates from Pailin (median, 13.5%) than in those from Ratanakiri (median, 0.8%), while exposed mature stages were equally and highly susceptible (0.6% and 0.7%, respectively). Ring stages survived drug exposure by cell cycle arrest and resumed growth upon drug withdrawal. The reduced susceptibility to artemisinin in Pailin appears to be associated with an altered in vitro phenotype of ring stages from Pailin in the RSA. |
Szelechowski, Marion; Bergeron, Corinne; Gonzalez-Dunia, Daniel; Klonjkowski, Bernard Production and Purification of Non Replicative Canine Adenovirus Type 2 Derived Vectors Article de journal Dans: JoVE, no. 82, 2013, ISSN: 1940-087X. @article{Szelechowski2013,
title = {Production and Purification of Non Replicative Canine Adenovirus Type 2 Derived Vectors},
author = {Marion Szelechowski and Corinne Bergeron and Daniel Gonzalez-Dunia and Bernard Klonjkowski},
doi = {10.3791/50833},
issn = {1940-087X},
year = {2013},
date = {2013-00-00},
urldate = {2013-00-00},
journal = {JoVE},
number = {82},
publisher = {MyJove Corporation},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
de Koning, H D; van den Bogaard, E H; Bergboer, J G M; Kamsteeg, M; van Vlijmen-Willems, I M J J; Hitomi, K; Henry, J; Simon, M; Takashita, N; Ishida-Yamamoto, A; Schalkwijk, J; Zeeuwen, P L J M Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair. Article de journal Dans: The British journal of dermatology, vol. 166, no. 6, p. 1245–1254, 2012, ISSN: 1365-2133 (Electronic). @article{DeKoning2012,
title = {Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair.},
author = {de Koning, H D and van den Bogaard, E H and Bergboer, J G M and Kamsteeg, M and van Vlijmen-Willems, I M J J and Hitomi, K and Henry, J and Simon, M and Takashita, N and Ishida-Yamamoto, A and Schalkwijk, J and Zeeuwen, P L J M},
doi = {10.1111/j.1365-2133.2012.10885.x},
issn = {1365-2133 (Electronic)},
year = {2012},
date = {2012-06-01},
journal = {The British journal of dermatology},
volume = {166},
number = {6},
pages = {1245--1254},
abstract = {BACKGROUND: Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope protein expression have been performed. OBJECTIVES: To analyse the effect of experimental skin barrier disruption on the expression of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins. METHODS: We examined mRNA (day 1, 3 and 7) and protein (day 1, 2, 4 and 9) expression levels of structural proteins and regulatory molecules after sodium dodecyl sulphate (SDS) application on normal skin, and tape stripping of uninvolved epidermis of patients with psoriasis and AD and healthy controls. RESULTS: Upon tape stripping, several structural molecules were significantly downregulated (at the mRNA level as well as the protein level), including LCE5A, LCE2B, FLG, FLG2 and LOR, whereas others were upregulated: IVL, SPRR1, SPRR2, HRNR and most notably LCE3A. The epidermal crosslinking enzymes TGM1, TGM3 and TGM5 were all upregulated, whereas proteases involved in the desquamation process (CTSV, KLK5 and KLK7) were downregulated or unaffected. Most results were similar in SDS-instigated irritant contact dermatitis. There was no significant difference in response between normal epidermis and nonlesional skin of patients with psoriasis and AD. CONCLUSIONS: Skin barrier disruption induces a temporary barrier repair response composed of increased expression of several cornification-related proteins, and decreased expression of some structural and desquamation-related proteins.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope protein expression have been performed. OBJECTIVES: To analyse the effect of experimental skin barrier disruption on the expression of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins. METHODS: We examined mRNA (day 1, 3 and 7) and protein (day 1, 2, 4 and 9) expression levels of structural proteins and regulatory molecules after sodium dodecyl sulphate (SDS) application on normal skin, and tape stripping of uninvolved epidermis of patients with psoriasis and AD and healthy controls. RESULTS: Upon tape stripping, several structural molecules were significantly downregulated (at the mRNA level as well as the protein level), including LCE5A, LCE2B, FLG, FLG2 and LOR, whereas others were upregulated: IVL, SPRR1, SPRR2, HRNR and most notably LCE3A. The epidermal crosslinking enzymes TGM1, TGM3 and TGM5 were all upregulated, whereas proteases involved in the desquamation process (CTSV, KLK5 and KLK7) were downregulated or unaffected. Most results were similar in SDS-instigated irritant contact dermatitis. There was no significant difference in response between normal epidermis and nonlesional skin of patients with psoriasis and AD. CONCLUSIONS: Skin barrier disruption induces a temporary barrier repair response composed of increased expression of several cornification-related proteins, and decreased expression of some structural and desquamation-related proteins. |