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Search Results: 1 - 10 of 3488 matches for " Ermanno Candolfi equal contributor "
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Severe South American Ocular Toxoplasmosis Is Associated with Decreased Ifn-γ/Il-17a and Increased Il-6/Il-13 Intraocular Levels
Alejandra de-la-Torre,Arnaud Sauer,Alexander W. Pfaff,Tristan Bourcier,Julie Brunet,Claude Speeg-Schatz,Laurent Ballonzoli,Odile Villard,Daniel Ajzenberg,Natarajan Sundar,Michael E. Grigg,Jorge E. Gomez-Marin equal contributor,Ermanno Candolfi equal contributor
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002541
Abstract: In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ.
Immunopathology in ocular toxoplasmosis: facts and clues
Garweg, Justus G;Candolfi, Ermanno;
Memórias do Instituto Oswaldo Cruz , 2009, DOI: 10.1590/S0074-02762009000200014
Abstract: although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (ot), the severity of the disease is probably correlated with hypersensitivity and inflammation. notwithstanding, the mechanisms that regulate the inflammatory process in recurrent ot are poorly understood. recent evidence has identified interleukin (il) 17 as a marker for disease severity. the ocular and cerebral presence of this cytokine is generally associated with the induction of autoimmune responses in the brain and the eye. indeed, there are indications that autoimmunity may contribute to clinical variability in the activity of ot. il-23, which induces the proliferation of il-17-producing cells and il-27, which is a counterplayer to il-17, may regulate t(h)-1-cell-mediated responses in ot. the importance of these cytokines in experimental models of uveitis and encephalitis has been recently reported. cd25(+) regulatory t-cells may control the local inflammatory response and protect the host against collateral inflammatory tissue damage. the responses of these cells to ot may be suitably tailored to cope with either an acquired or a congenital aetiology. knowledge relating to immunoreactivity in ot has grown impressively during the past few years. its characteristic and variable features have been identified and the potential relevance of autoimmunity has been assessed. in light of this knowledge, potential future treatment options have been considered.
A First Human Case of Ocular Dirofilariosis due to Dirofilaria repens in Northeastern France
Nicolas Argy,Marcela Sabou,Alain Billing,Christian Hermsdorff,Ermanno Candolfi,Ahmed Abou-Bacar
Journal of Tropical Medicine , 2011, DOI: 10.1155/2011/698647
Abstract: We report the first case of ocular dirofilariasis to be diagnosed in northeast France (Alsace region), in a man who presented with a suborbital mass after a journey to Senegal. Microscopic examination of the surgical specimen identified Dirofilaria repens. 1. Introduction Dirofilariasis is a zoonosis occasionally associated with orbital floor infection. The natural definitive hosts are dogs and, more rarely, cats [1–3]. The adult female nematode usually lives in the heart or subcutaneous tissues and sheds microfilariae into the bloodstream [2–4]. The microfilariae are then transmitted by Culex, Aedes, or Anopheles mosquitoes, which are also intermediate hosts [1, 2, 4]. Humans are a dead-end host for this nematode, which can cause pulmonary, ocular, or subcutaneous lesions [2, 5–8]. Human orbital dirofilariasis is uncommon. Such patients may present with cysts resembling benign or malignant eye tumors [3, 9]. We report the first case of ocular dirofilariasis due to Dirofilaria repens to be diagnosed in Alsace, France. The patient presented with an inflammatory periorbital tumor-like lesion. 2. Case Report A 60-year-old man living in Rosheim, Alsace (northeast France) presented with a nodule on the left orbital floor on 8 July 2008. His only recent travel was to Casamance, southern Senegal, in April 2008. Physical examination showed a palpable nodular lesion of the left orbital floor, while magnetic resonance imaging showed an inflammatory nodular lesion. Inflammatory cholangioma, eyelid lymphoedema, or allergies were considered as possible diagnoses. Antibiotic and steroid therapy had no impact on his symptoms, and the nodule was surgically removed in September 2008. It measured 5?cm along its longest axis. Microscopically, it consisted of polymorphic inflammatory granuloma tissue containing plasmocytes and eosinophilic polymorphonuclear cells, with an epitheliogigantocellular granuloma surrounding a nematode cross-section (Figure 1(a)). The surgical specimen was transferred to our laboratory (Laboratoire de Parasitologie et Mycologie Médicale de Strasbourg) for precise identification of the parasite. The nematode cross-section was composed of a thick laminated cuticle with external longitudinal ridges. A polymyarian muscle fiber was visible, surrounded by a pseudocoelomic cavity. Lateral chords and male gonads were visible in some other sections (Figure 1(b)). Ocular infection by an immature male Dirofilaria repens nematode was diagnosed. The patient made a full recovery after surgery, and no further treatment was required. Figure 1: (a) Inflammatory
Icacina senegalensis (Icacinaceae), traditionally used for the treatment of malaria, inhibits in vitro Plasmodium falciparum growth without host cell toxicity
Serigne O Sarr, Sylvie Perrotey, Ibrahima Fall, Sa?d Ennahar, Minjie Zhao, Yérim M Diop, Ermanno Candolfi, Eric Marchioni
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-85
Abstract: Different concentrations of the plant extract and fractions were tested on synchronized Plasmodium falciparum cultures at the ring stage using the parasite lactate dehydrogenase assay. Their haemolytic activity and in vitro cytoxicity were evaluated. The chromatographic profiles of active fractions were also established.The plant extract and fractions revealed anti-plasmodial activity (IC50 < 5 μg/mL) with no toxicity (Selectivity indexes >10). The dichloromethane fraction showed stronger anti-plasmodial activity than the total extract.Anti-plasmodial activity and toxicity of I. senegalensis are reported for the first time and showed promising results in malaria field research.Despite intensive efforts to control malaria, the disease continues to be one of the greatest health problems facing Africa [1]. Then the global scope of malaria and the spread of drug-resistant Plasmodium falciparum make the need for improved therapy undeniable. There were an estimated 247 million malaria cases among 3.3 billion people at risk in 2006, causing nearly one million deaths, mostly children under five years of age. One hundred six countries were endemic for malaria in 2009, 45 within the WHO African region [1].This worsening situation can be explained by resistance of P. falciparum to the current anti-malarial drugs [2], lack of new therapeutic targets, unaffordability and poor quality of anti-malarial drugs [3,4] and their bad storage under tropical conditions [4]. Then an urgent need for the development of new anti-malarial agents faces the scientific community.Traditional medical knowledge based on the use of natural products from plants has often been the basis for discovering new drugs. It is estimated that 80% of many developing countries population still use plant-based traditional medicines [5]. These natural products and their derivatives represent almost half of the drugs approved since 1994 [6] and more than 30% of the current anti-malarial market [7].In this context, a
Identification of a New Rhoptry Neck Complex RON9/RON10 in the Apicomplexa Parasite Toxoplasma gondii
Mauld H. Lamarque, Julien Papoin, Anne-Laure Finizio, Gaelle Lentini, Alexander W. Pfaff, Ermanno Candolfi, Jean-Fran?ois Dubremetz, Maryse Lebrun
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032457
Abstract: Apicomplexan parasites secrete and inject into the host cell the content of specialized secretory organelles called rhoptries, which take part into critical processes such as host cell invasion and modulation of the host cell immune response. The rhoptries are structurally and functionally divided into two compartments. The apical duct contains rhoptry neck (RON) proteins that are conserved in Apicomplexa and are involved in formation of the moving junction (MJ) driving parasite invasion. The posterior bulb contains rhoptry proteins (ROPs) unique to an individual genus and, once injected in the host cell act as effector proteins to co-opt host processes and modulate parasite growth and virulence. We describe here two new RON proteins of Toxoplasma gondii, RON9 and RON10, which form a high molecular mass complex. In contrast to the other RONs described to date, this complex was not detected at the MJ during invasion and therefore was not associated to the MJ complex RON2/4/5/8. Disruptions of either RON9 or RON10 gene leads to the retention of the partner in the ER followed by subsequent degradation, suggesting that the RON9/RON10 complex formation is required for proper sorting to the rhoptries. Finally, we show that the absence of RON9/RON10 has no significant impact on the morphology of rhoptry, on the invasion and growth in fibroblasts in vitro or on virulence in vivo. The conservation of RON9 and RON10 in Coccidia and Cryptosporidia suggests a specific relation with development in intestinal epithelial cells.
A new ELISA kit which uses a combination of Plasmodium falciparum extract and recombinant Plasmodium vivax antigens as an alternative to IFAT for detection of malaria antibodies
Cecile Doderer, Aurelie Heschung, Phillippe Guntz, Jean-Pierre Cazenave, Yves Hansmann, Alexandre Senegas, Alexander W Pfaff, Tamer Abdelrahman, Ermanno Candolfi
Malaria Journal , 2007, DOI: 10.1186/1475-2875-6-19
Abstract: Two groups were used: 95 samples from malaria patients to assess the clinical sensitivity and 2,152 samples from blood donors, who had not been exposed to malaria, to assess the clinical specificity.The DiaMed ELISA test kit had a clinical sensitivity of 84.2% and a clinical specificity of 99.6% as compared with 70.5% and 99.6% respectively, using the IFAT method. The ELISA method was more sensitive than the IFAT method for P. vivax infections (75% vs. 25%). However, in 923 malaria risk donors the analytical sensitivity of the ELISA test was 40% and its specificity 98.3%, performances impaired by large numbers of equivocal results non-concordant between ELISA and IFAT. When the overall analytical performances of ELISA was compared to IFAT, the ELISA efficiency J index was 0.84 versus 0.71 for IFAT. Overall analytical sensitivity was 93.1% and the analytical specificity 96.7%. Overall agreement between the two methods reached 0.97 with a reliability k index of 0.64.The DiaMed ELISA test kit shows a good correlation with IFAT for analytical and clinical parameters. It may be an interesting method to replace the IFAT especially in blood banks, but further extensive investigations are needed to examine the analytical performance of the assay, especially in a blood bank setting.More than 2 billion people (40% of the world's population) live in areas where malaria is endemic. It was estimated that over 250 million people worldwide contracted malaria in 2002 [1]. Following infection with any of the four species of Plasmodium, specific antibodies are produced, in virtually all individuals, one or two weeks after initial infection and persist for three to six months after parasite clearance. These antibodies may persist for months or years in semi-immune patients in endemic countries where reinfection is frequent. However, in a non-immune patient, treated for a single infection, antibody levels fall more rapidly and may be undetectable by three to six months. Reinfection or
Human-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication
Thomas Cherrier, Mikael Elias, Alicia Jeudy, Guillaume Gotthard, Valentin Le Douce, Houda Hallay, Patrick Masson, Andrea Janossy, Ermanno Candolfi, Olivier Rohr, Eric Chabrière, Christian Schwartz
Virology Journal , 2011, DOI: 10.1186/1743-422x-8-352
Abstract: Human immunodeficiency 1 (HIV-1), identified in 1983 [1], remains a global health threat responsible for a world-wide pandemic. The introduction of the highly active antiretroviral therapy (HAART) in 1996 exhibited the potential of curing acquired immune deficiency syndrome (AIDS). Even though an effective AIDS vaccine is still lacking, HAART has greatly extended survival [2]. AIDS pandemic has stabilized on a global scale in 2008 with an estimated 33 million people infected worldwide (data from UN, 2008).However, several problems have been encountered since the introduction of HAART, and improvements in the design of drugs for HIV-1 are needed. A drawback of HAART is that the treatment is very expensive with limitation of its use to western countries. HAART has also several serious side effects leading to treatment interruption. Another major concern is related to the emergence of multidrug resistant viruses which has been reported in patients receiving HAART [3-5]. Therefore, new antiviral drugs are needed with activities against both wild type and mutant viruses. Two major cellular targets for HIV-1 are currently known which have critical role in HIV pathogenesis, i.e. CD4+ T lymphocytes and monocytes/macrophages including microglial cells, which are the central nervous system resident macrophages [6-8]. However, several drugs being active in CD4+ T lymphocytes are ineffective in chronically infected macrophages (i.e. several reverse transcriptase inhibitors) [9], and protease inhibitors have significantly lower activities in macrophages compared to lymphocytes [10]. Finally, many observations strongly suggest that even long term suppression of HIV-1 replication by HAART cannot totally eliminate HIV-1. The virus persists in cellular reservoirs because of viral latency, cryptic ongoing replication or poor drug penetration [11-13]. Moreover, these cellular reservoirs are often found in tissue sanctuary sites where penetration of drugs is restricted, like in the bra
Inter-Cellular Variation in DNA Content of Entamoeba histolytica Originates from Temporal and Spatial Uncoupling of Cytokinesis from the Nuclear Cycle
Chandrama Mukherjee equal contributor,Shubhra Majumder equal contributor,Anuradha Lohia
PLOS Neglected Tropical Diseases , 2009, DOI: 10.1371/journal.pntd.0000409
Abstract: Accumulation of multiple copies of the genome in a single nucleus and several nuclei in a single cell has previously been noted in Entamoeba histolytica, contributing to the genetic heterogeneity of this unicellular eukaryote. In this study, we demonstrate that this genetic heterogeneity is an inherent feature of the cell cycle of this organism. Chromosome segregation occurs on a variety of novel microtubular assemblies including multi-polar spindles. Cytokinesis in E. histolytica is completed by the mechanical severing of a thin cytoplasmic bridge, either independently or with the help of neighboring cells. Importantly, cytokinesis is uncoupled from the nuclear division cycle, both temporally and spatially, leading to the formation of unequal daughter cells. Sorting of euploid and polyploid cells showed that each of these sub-populations acquired heterogeneous DNA content upon further growth. Our study conclusively demonstrates that genetic heterogeneity originates from the unique mode of cell division events in this protist.
Hypersensitive to Red and Blue 1 and Its Modification by Protein Phosphatase 7 Are Implicated in the Control of Arabidopsis Stomatal Aperture
Xiaodong Sun equal contributor,Xiaojun Kang equal contributor,Min Ni
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002674
Abstract: The stomatal pores are located on the plant leaf epidermis and regulate CO2 uptake for photosynthesis and the loss of water by transpiration. Their stomatal aperture therefore affects photosynthesis, water use efficiency, and agricultural crop yields. Blue light, one of the environmental signals that regulates the plant stomatal aperture, is perceived by the blue/UV-A light-absorbing cryptochromes and phototropins. The signal transduction cascades that link the perception of light to the stomatal opening response are still largely unknown. Here, we report two new players, Hypersensitive to Red and Blue 1 (HRB1) and Protein Phosphatase 7 (PP7), and their genetic and biochemical interactions in the control of stomatal aperture. Mutations in either HRB1 or PP7 lead to the misregulation of the stomatal aperture and reduce water loss under blue light. Both HRB1 and PP7 are expressed in the guard cells in response to a light-to-dark or dark-to-light transition. HRB1 interacts with PP7 through its N-terminal ZZ-type zinc finger motif and requires a functional PP7 for its stomatal opening response. HRB1 is phosphorylated in vivo, and PP7 can dephosphorylate HRB1. HRB1 is mostly dephosphorylated in a protein complex of 193 kDa in the dark, and blue light increases complex size to 285 kDa. In the pp7 mutant, this size shift is impaired, and HRB1 is predominately phosphorylated. We propose that a modification of HRB1 by PP7 under blue light is essential to acquire a proper conformation or to bring in new components for the assembly of a functional HRB1 protein complex. Guard cells control stomatal opening in response to multiple environmental or biotic stimuli. This study may furnish strategies that allow plants to enjoy the advantages of both constitutive and ABA-induced protection under water-limiting conditions.
Kinetics of Mosquito-Injected Plasmodium Sporozoites in Mice: Fewer Sporozoites Are Injected into Sporozoite-Immunized Mice
Chahnaz Kebaier equal contributor,Tatiana Voza equal contributor,Jerome Vanderberg
PLOS Pathogens , 2009, DOI: 10.1371/journal.ppat.1000399
Abstract: Malaria is initiated when the mosquito introduces sporozoites into the skin of a mammalian host. To successfully continue the infection, sporozoites must invade blood vessels in the dermis and be transported to the liver. A significant number of sporozoites, however, may enter lymphatic vessels in the skin or remain in the skin long after the mosquito bite. We have used fluorescence microscopy of Plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the kinetics of sporozoite disappearance from the skin. Sporozoites injected into immunized mice were rapidly immobilized, did not appear to invade dermal blood vessels and became morphologically degraded within several hours. Strikingly, mosquitoes introduced significantly fewer sporozoites into immunized than into non-immunized mice, presumably by formation of an immune complex between soluble sporozoite antigens in the mosquito saliva and homologous host antibodies at the proboscis tip. These results indicate that protective antibodies directed against sporozoites may function both by reducing the numbers of sporozoites injected into immunized hosts and by inhibiting the movement of injected sporozoites into dermal blood vessels.
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