@article{b,

title = {Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles from Cameroonian isolates},

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

year  = {2016},

date = {2016-01-01},

journal = {Malar J},

volume = {15},

number = {1},

pages = {572},

abstract = {BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa. Here, the k13-propeller polymorphism was compared to both ex vivo susceptibility to DHA and early parasitological and clinical responses to artemisinin combination therapy (ACT). METHODS: Plasmodium falciparum isolates were collected in 2015 in Yaounde (Cameroon) from patients treated with dihydroartemisinin-piperaquine combination. Samples were analysed for their susceptibility to artemisinin using the k13-propeller sequencing, the ex vivo ring-stage survival assay, the in vivo parasite positive rate and the clinical statute at day 2. RESULTS: None of the collected isolates revealed the presence of resistance mutations in the k13-propeller sequence. The median ring-stage survival rate for all the 64 interpretable isolates after a 6-hour pulse of 700 nM dihydroartemisinin was low, 0.49% (IQR: 0-1.3). Total parasite clearance was observed for 87.5% of patients and the remaining parasitaemic isolates (12.5%) showed a high reduction of parasite load, ranging from 97.5 to 99.9%. Clinical symptoms disappeared in 92.8% of cases. CONCLUSION: This study demonstrated the absence of k13-resistant genotypes in P. falciparum isolates from Cameroon. Only synonymous mutations were found with a low prevalence (4.3%). A good association between k13 genotypes and the ex vivo ring-stage survival assay or parasitological and clinical data was obtained. These results give a baseline for the long-term monitoring of artemisinin derivative efficacy in Africa.},

note = {Nov 26;15(1):572.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{b,

title = {Transnuclear CD8 T cells specific for the immunodominant epitope Gra6 lower acute-phase Toxoplasma gondii burden},

author = {Sanecka, A. and Yoshida, N. and Dougan, S. K. and Jackson, J. and Shastri, N. and Ploegh, H. and Blanchard, N. and Frickel, E. M.},

year  = {2016},

date = {2016-01-01},

journal = {Immunology},

abstract = {We generated a CD8 T-cell receptor (TCR) transnuclear (TN) mouse specific to the Ld -restricted immunodominant epitope of GRA6 from Toxoplasma gondii as a source of cells to facilitate further investigation into the CD8 T-cell-mediated response against this pathogen. The TN T cells bound Ld -Gra6 tetramer and proliferated upon unspecific and peptide-specific stimulation. The TCR beta sequence of the Gra6-specific TN CD8 T cells is identical in its V- and J-region to the TCR-beta harboured by a hybridoma line generated in response to Gra6 peptide. Adoptively transferred Gra6 TN CD8 T cells proliferated upon Toxoplasma infection in vivo and exhibited an activated phenotype similar to host CD8 T cells specific to Gra6. The brain of Toxoplasma-infected mice carried Gra6 TN cells already at day 8 post-infection. Both Gra6 TN mice as well as adoptively transferred Gra6 TN cells were able to significantly reduce the parasite burden in the acute phase of Toxoplasma infection. Overall, the Gra6 TN mouse represents a functional tool to study the protective and immunodominant specific CD8 T-cell response to Toxoplasma in both the acute and the chronic phases of infection.},

note = {Jul 5. doi: 10.1111/imm.12643.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{b,

title = {An epidemiologically successful Escherichia coli sequence type modulates Plasmodium falciparum infection in the mosquito midgut},

author = {Tchioffo, M. T. and Abate, L. and Boissiere, A. and Nsango, S. E. and Gimonneau, G. and Berry, A. and Oswald, E. and Dubois, D. and Morlais, I.},

year  = {2016},

date = {2016-01-01},

journal = {Infect Genet Evol},

volume = {43},

pages = {22-30},

abstract = {Malaria transmission relies on the successful development of Plasmodium parasites in the Anopheles mosquito vector. Within the mosquito midgut, malaria parasites encounter a resident bacterial flora and parasite-bacteria interactions modulate Plasmodium development. The mechanisms by which the bacteria interact with malaria parasites are still unknown. The intestinal microbiota could regulate immune signaling pathways or produce bacterial compounds that block Plasmodium development. In this study, we characterized Escherichia coli strains previously isolated from the Anopheles mosquito midgut and investigated the putative role of two E. coli clones, 444ST95 and 351ST73, on parasite development. Sporogonic development was significantly impacted by exposure to clone 444ST95 whereas prevalence and intensity of infection were not different in mosquitoes challenged with 351ST73 as compared to control mosquitoes. This result indicates midgut bacteria exhibit intra-specific variation in their ability to inhibit Plasmodium development. Expression patterns of immune genes differed between mosquitoes challenged with 444ST95 and 351ST73 and examination of the luminal midgut surface by transmission electron microscopy revealed distinct effects of bacterial exposure on midgut epithelial cells. The 444ST95 clone strongly affected mosquito survival and parasite development and this could be associated to the Hemolysin F or other toxins released by the bacteria. Further studies will be needed to decipher the virulence factors and to determine their contribution to the observed phenotype of the 444ST95E. coli strain that belongs to the epidemiological ST95 clonal group responsible for extra intestinal infections in human and other animals.},

note = {Sep;43:22-30. doi: 10.1016/j.meegid.2016.05.002. Epub 2016 May 3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN10b,

title = {CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model},

author = {Yshii, L. M. and Gebauer, C. M. and Pignolet, B. and Maure, E. and Queriault, C. and Pierau, M. and Saito, H. and Suzuki, N. and Brunner-Weinzierl, M. and Bauer, J. and Liblau, R.},

url = {http://www.ncbi.nlm.nih.gov/pubmed/27604307},

doi = {10.1093/brain/aww225},

issn = {1460-2156 (Electronic) 

0006-8950 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Brain},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN17b,

title = {Foxo3 Transcription Factor Drives Pathogenic T Helper 1 Differentiation by Inducing the Expression of Eomes},

author = {Stienne, C. and Michieletto, M. F. and Benamar, M. and Carrie, N. and Bernard, I. and Nguyen, X. H. and Lippi, Y. and Duguet, F. and Liblau, R. S. and Hedrick, S. M. and Saoudi, A. and Dejean, A. S.},

url = {http://www.ncbi.nlm.nih.gov/pubmed/27742544},

doi = {10.1016/j.immuni.2016.09.010},

issn = {1097-4180 (Electronic) 

1074-7613 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Immunity},

volume = {45},

number = {4},

pages = {774-787},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN28b,

title = {Zika virus in semen and spermatozoa},

author = {Mansuy, J. M. and Suberbielle, E. and Chapuy-Regaud, S. and Mengelle, C. and Bujan, L. and Marchou, B. and Delobel, P. and Gonzalez-Dunia, D. and Malnou, C. E. and Izopet, J. and Martin-Blondel, G.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27676340},

doi = {10.1016/S1473-3099(16)30336-X},

issn = {1474-4457 (Electronic) 

1473-3099 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Lancet Infect Dis},

volume = {16},

number = {10},

pages = {1106-1107},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN29b,

title = {Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen?},

author = {Mansuy, J. M. and Dutertre, M. and Mengelle, C. and Fourcade, C. and Marchou, B. and Delobel, P. and Izopet, J. and Martin-Blondel, G.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26949027},

doi = {10.1016/S1473-3099(16)00138-9},

issn = {1474-4457 (Electronic) 

1473-3099 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Lancet Infect Dis},

volume = {16},

number = {4},

pages = {405},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN11b,

title = {High-dimensional single-cell analysis reveals the immune signature of narcolepsy},

author = {Hartmann, F. J. and Bernard-Valnet, R. and Queriault, C. and Mrdjen, D. and Weber, L. M. and Galli, E. and Krieg, C. and Robinson, M. D. and Nguyen, X. H. and Dauvilliers, Y. and Liblau, R. S. and Becher, B.},

url = {http://www.ncbi.nlm.nih.gov/pubmed/27821550},

doi = {10.1084/jem.20160897},

issn = {1540-9538 (Electronic) 

0022-1007 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {J Exp Med},

volume = {213},

number = {12},

pages = {2621-2633},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN34b,

title = {In situ expansion of T cells that recognize distinct self-antigens sustains autoimmunity in the CNS},

author = {Ramadan, A. and Lucca, L. E. and Carrie, N. and Desbois, S. and Axisa, P. P. and Hayder, M. and Bauer, J. and Liblau, R. S. and Mars, L. T.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27000832},

doi = {10.1093/brain/aww032},

issn = {1460-2156 (Electronic) 

0006-8950 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Brain},

volume = {139},

number = {Pt 5},

pages = {1433-46},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN38,

title = {Thymus-Derived Regulatory T Cells Are Positively Selected on Natural Self-Antigen through Cognate Interactions of High Functional Avidity},

author = {Kieback, E. and Hilgenberg, E. and Stervbo, U. and Lampropoulou, V. and Shen, P. and Bunse, M. and Jaimes, Y. and Boudinot, P. and Radbruch, A. and Klemm, U. and Kuhl, A. A. and Liblau, R. and Hoevelmeyer, N. and Anderton, S. M. and Uckert, W. and Fillatreau, S.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27192577},

doi = {10.1016/j.immuni.2016.04.018},

issn = {1097-4180 (Electronic) 

1074-7613 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Immunity},

volume = {44},

number = {5},

pages = {1114-26},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN39b,

title = {High-dimensional single-cell analysis reveals the immune signature of narcolepsy},

author = {Hartmann, F. J. and Bernard-Valnet, R. and Queriault, C. and Mrdjen, D. and Weber, L. M. and Galli, E. and Krieg, C. and Robinson, M. D. and Nguyen, X. H. and Dauvilliers, Y. and Liblau, R. S. and Becher, B.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27821550},

doi = {10.1084/jem.20160897},

issn = {1540-9538 (Electronic) 

0022-1007 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {J Exp Med},

volume = {213},

number = {12},

pages = {2621-2633},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN37b,

title = {Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells},

author = {Aloulou, M. and Carr, E. J. and Gador, M. and Bignon, A. and Liblau, R. S. and Fazilleau, N. and Linterman, M. A.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26818004},

doi = {10.1038/ncomms10579},

issn = {2041-1723 (Electronic) 

2041-1723 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Nat Commun},

volume = {7},

pages = {10579},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN10b,

title = {CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model},

author = {Yshii, L. M. and Gebauer, C. M. and Pignolet, B. and Maure, E. and Queriault, C. and Pierau, M. and Saito, H. and Suzuki, N. and Brunner-Weinzierl, M. and Bauer, J. and Liblau, R.},

url = {http://www.ncbi.nlm.nih.gov/pubmed/27604307},

doi = {10.1093/brain/aww225},

issn = {1460-2156 (Electronic) 

0006-8950 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Brain},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Starkl2016,

title = {IgE antibodies, Fc$epsilon$RI$alpha$, and IgE-mediated local anaphylaxis can limit snake venom toxicity.},

author = {Starkl, Philipp and Marichal, Thomas and Gaudenzio, Nicolas and Reber, Laurent Lionel and Sibilano, Riccardo and Tsai, Mindy and Galli, Stephen Joseph},

doi = {10.1016/j.jaci.2015.08.005},

issn = {1097-6825 (Electronic)},

year  = {2016},

date = {2016-01-01},

journal = {The Journal of allergy and clinical immunology},

volume = {137},

number = {1},

pages = {246--257.e11},

abstract = {BACKGROUND: Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. OBJECTIVE: We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. METHODS: We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. RESULTS: A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional Fc$epsilon$RI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. CONCLUSION: These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dalmeida_ecto-atpdase_2016,

title = {The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27},

author = {d'Almeida, Sènan M. and Kauffenstein, Gilles and Roy, Charlotte and Basset, Laetitia and Papargyris, Loukas and Henrion, Daniel and Catros, Véronique and Ifrah, Norbert and Descamps, Philippe and Croue, Anne and Jeannin, Pascale and Grégoire, Marc and Delneste, Yves and Tabiasco, Julie},

doi = {10.1080/2162402X.2016.1178025},

issn = {2162-4011},

year  = {2016},

date = {2016-01-01},

journal = {Oncoimmunology},

volume = {5},

number = {7},

pages = {e1178025},

abstract = {Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{chene_pleural_2016,

title = {Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages},

author = {Chéné, Anne-Laure and d'Almeida, Sènan and Blondy, Thibaut and Tabiasco, Julie and Deshayes, Sophie and Fonteneau, Jean-François and Cellerin, Laurent and Delneste, Yves and Grégoire, Marc and Blanquart, Christophe},

doi = {10.1016/j.jtho.2016.06.022},

issn = {1556-1380},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer},

volume = {11},

number = {10},

pages = {1765--1773},

abstract = {INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties. 

METHODS: The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and enzyme-linked immunosorbent assay. Immunohistochemical analysis was used to support the results. Cocultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment. 

RESULTS: We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (high CD14, high CD163, and interleukin-10 secretion after activation). The colony-stimulating factor 1 receptor/macrophage colony-stimulating factor (M-CSF) pathway is implicated in M2 polarization, and high levels of M-CSF were measured in MPM samples compared with benign PE (4.17 ± 2.75 ng/mL and 1.94 ± 1.47 ng/mL, respectively). Immunohistochemical analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment. 

CONCLUSIONS: These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and colony-stimulating factor 1 receptor/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vidal_are_2016,

title = {Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?},

author = {Vidal, Fabien and Guerby, Paul and Luyckx, Mathieu and Haddad, Pascale and Stoeckle, Eberhard and Morice, Philippe and Leblanc, Eric and Lecuru, Fabrice and Daraï, Emile and Classe, Jean Marc and Pomel, Christophe and Filleron, Thomas and Ferron, Gwenael and Querleu, Denis and Rafii, Arash},

doi = {10.1371/journal.pone.0147787},

issn = {1932-6203},

year  = {2016},

date = {2016-01-01},

journal = {PloS One},

volume = {11},

number = {1},

pages = {e0147787},

abstract = {OBJECTIVE: Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. 

STUDY DESIGN: We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. RESULTS: The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{deschemin_microbiota_2016,

title = {The microbiota shifts the iron sensing of intestinal cells},

author = {Deschemin, Jean-Christophe and Noordine, Marie-Louise and Remot, Aude and Willemetz, Alexandra and Afif, Clément and Canonne-Hergaux, François and Langella, Philippe and Karim, Zoubida and Vaulont, Sophie and Thomas, Muriel and Nicolas, Gaël},

doi = {10.1096/fj.15-276840},

issn = {1530-6860},

year  = {2016},

date = {2016-01-01},

journal = {FASEB journal: official publication of the Federation of American Societies for Experimental Biology},

volume = {30},

number = {1},

pages = {252--261},

abstract = {The amount of iron in the diet directly influences the composition of the microbiota. Inversely, the effects of the microbiota on iron homeostasis have been little studied. So, we investigate whether the microbiota itself may alter host iron sensing. Duodenal cytochrome b and divalent metal transporter 1, involved in apical iron uptake, are 8- and 10-fold, respectively, more abundant in the duodenum of germ-free (GF) mice than in mice colonized with a microbiota. In contrast, the luminal exporter ferroportin is 2-fold less abundant in GF. The overall signature of microbiota on iron-related proteins is similar in the colon. The colonization does not modify systemic parameters as plasma transferrin saturation (20%), plasma ferritin (150 ng/L), and liver (85 µg/g) iron load. Commensal organisms (Bacteroides thetaiotaomicron VPI-5482 and Faecalibacterium prausnitzii A2-165) and a probiotic strain (Streptococcus thermophilus LMD-9) led to up to 12-fold induction of ferritin in colon. Our data suggest that the intestinal cells of GF mice are depleted of iron and that following colonization, the epithelial cells favor iron storage. This study is the first to demonstrate that gut microbes induce a specific iron-related protein signature, highlighting new aspects of the crosstalk between the microbiota and the intestinal epithelium.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Different activation signals induce distinct mast cell degranulation strategies},

author = {Gaudenzio, N. and Sibilano, R. and Marichal, T. and Starkl, P. and Reber, L. L. and Cenac, N. and McNeil, B. D. and Dong, X. and Hernandez, J. D. and Sagi-Eisenberg, R. and Hammel, I. and Roers, A. and Valitutti, S. and Tsai, M. and Espinosa, E. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {J Clin Invest},

volume = {126},

number = {10},

pages = {3981-3998},

abstract = {Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P-dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation.},

note = {Gaudenzio, Nicolas 

Sibilano, Riccardo 

Marichal, Thomas 

Starkl, Philipp 

Reber, Laurent L 

Cenac, Nicolas 

McNeil, Benjamin D 

Dong, Xinzhong 

Hernandez, Joseph D 

Sagi-Eisenberg, Ronit 

Hammel, Ilan 

Roers, Axel 

Valitutti, Salvatore 

Tsai, Mindy 

Espinosa, Eric 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

P30 NS069375/NS/NINDS NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

S10 RR026780/RR/NCRR NIH HHS/United States 

J Clin Invest. 2016 Oct 3;126(10):3981-3998. doi: 10.1172/JCI85538. Epub 2016 Sep 19.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse},

author = {Khazen, R. and Müller, S. and Gaudenzio, N. and Espinosa, E. and Puissegur, M. P. and Valitutti, S.},

year  = {2016},

date = {2016-01-01},

journal = {Nat Commun},

volume = {7},

pages = {10823},

abstract = {Human melanoma cells express various tumour antigens that are recognized by CD8(+) cytotoxic T lymphocytes (CTLs) and elicit tumour-specific responses in vivo. However, natural and therapeutically enhanced CTL responses in melanoma patients are of limited efficacy. The mechanisms underlying CTL effector phase failure when facing melanomas are still largely elusive. Here we show that, on conjugation with CTL, human melanoma cells undergo an active late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration. Abortion of SNAP-23-dependent lysosomal trafficking, pH perturbation or impairment of lysosomal proteolytic activity restores susceptibility to CTL attack. Inside the arsenal of melanoma cell strategies to escape immune surveillance, we identify a self-defence mechanism based on exacerbated lysosome secretion and perforin degradation at the lytic synapse. Interfering with this synaptic self-defence mechanism might be useful in potentiating CTL-mediated therapies in melanoma patients.},

note = {Khazen, Roxana 

Müller, Sabina 

Gaudenzio, Nicolas 

Espinosa, Eric 

Puissegur, Marie-Pierre 

Valitutti, Salvatore 

Research Support, Non-U.S. Gov't 

Nat Commun. 2016 Mar 4;7:10823. doi: 10.1038/ncomms10823.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}