25 results on '"Valérie Gafa"'
Search Results
2. Impairment of neutrophil reactivity to elastin peptides in COPD
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Gaëtan Deslée, Frank Antonicelli, Aurélie Dupont, François Lebargy, Sandra Dury, Moncef Guenounou, Valérie Gafa, Richard Le Naour, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Pulmonary and Respiratory Medicine ,Neutrophils ,Phagocytosis ,Receptor expression ,Receptors, Cell Surface ,Inflammation ,Neutrophil Activation ,Proinflammatory cytokine ,Leukocyte Count ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,Aged ,030304 developmental biology ,0303 health sciences ,COPD ,Cell chemotaxis ,biology ,business.industry ,Chemotaxis ,Smoking ,Sputum ,Middle Aged ,Flow Cytometry ,medicine.disease ,Elastin ,respiratory tract diseases ,030228 respiratory system ,Immunology ,biology.protein ,Cytokines ,Female ,medicine.symptom ,Reactive Oxygen Species ,business - Abstract
Rationale Neutrophils play an important role in the inflammatory process associated with chronic obstructive pulmonary disease (COPD). Lung-infiltrating neutrophils secrete elastinolytic proteases that participate in elastin breakdown and the formation of elastin peptides (EPs). Objectives We hypothesized that circulating neutrophil-associated immune response may be modulated by EPs during COPD. Methods Neutrophils obtained from patients with either stable or exacerbated COPD and controls were cultured with or without EPs. Cell chemotaxis was analysed by the Boyden method and cytokine expression was analysed by ELISA and real-time reverse transcriptase PCR. Bacterial phagocytosis and killing of ingested bacteria were evaluated after incubation with Pseudomonas aeruginosa. Reactive oxygen species (ROS) measurement and elastin receptor expression were determined by flow cytometry. Results Chemotactic activity of neutrophils from patients with COPD towards the VGVAPG EP was reduced compared with controls. VGVAPG increased proinflammatory cytokine synthesis and bacterial load, but reduced ROS production in neutrophils from controls and from patients with stable COPD. Patients with exacerbated COPD were unresponsive to VGVAPG treatment. These findings were associated with a decreased or almost complete loss of S-Gal elastin receptor expression in neutrophils from patients with stable or exacerbated COPD, respectively. Conclusions The study demonstrates that the response of neutrophils from patients with COPD to VGVAPG varied according to COPD phase and critical level of S-Gal expression. S-Gal downregulation could result from a feedback mechanism induced by high levels of EPs.
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- 2013
3. EBV stimulates TLR- and autophagy-dependent pathways and impairs maturation in plasmacytoid dendritic cells: Implications for viral immune escape
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Eliana M. Coccia, Gian Maria Fimia, Valérie Gafa, Pankaj Trivedi, Elena Giacomini, Marco Corazzari, Alessandra Romagnoli, Fabiana Rizzo, Eleni Anastasiadou, and Martina Severa
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Immune system ,Viral replication ,Downregulation and upregulation ,Immunity ,Immunology ,Autophagy ,Immunology and Allergy ,hemic and immune systems ,Tumor necrosis factor alpha ,Biology ,Gene ,Virus - Abstract
Plasmacytoid DCs (pDCs) are crucial mediators in the establishment of immunity against most viruses, given their extraordinary capacity to produce a massive quantity of type I IFN. In this study we investigate the response of pDCs to infection with EBV, a γ-herpes virus that persists with an asymptomatic infection in immunocompetent hosts, although in certain conditions it can promote development of cancers or autoimmune diseases. We show that high amounts of type I IFNs were released from isolated pDCs after exposure to EBV by a mechanism requiring TLRs and a functional autophagic machinery. We next demonstrate that EBV can infect pDCs via viral binding to MHC class II molecule HLA-DR and that pDCs express EBV-induced latency genes. Furthermore, we observe that EBV is able to induce activation but not maturation of pDCs, which correlates with an impaired TNF-α release. Accordingly, EBV-infected pDCs are unable to mount a full T-cell response, suggesting that impaired pDC maturation, combined with a concomitant EBV-mediated upregulation of the T-cell inhibitory molecules B7-H1 and ICOS-L, could represent an immune-evasion strategy promoted by the virus. These mechanisms might lead to persistence in immunocompetent hosts or to dysregulated immune responses linked to EBV-associated diseases.
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- 2012
4. Enhancement of anti-Aspergillus T helper type 1 response by interferon-β-conditioned dendritic cells
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Elena Giacomini, Renée Grillot, Eliana M. Coccia, Maria Elena Remoli, Martina Severa, and Valérie Gafa
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CD86 ,biology ,medicine.medical_treatment ,Phagocytosis ,Immunology ,chemical and pharmacologic phenomena ,Immunotherapy ,Acquired immune system ,biology.organism_classification ,In vitro ,Microbiology ,Aspergillus fumigatus ,Immune system ,Antigen ,medicine ,Immunology and Allergy - Abstract
Although data show the importance of type I interferons (IFNs) in the regulation of the innate and adaptive immunity elicited in response to viral, bacterial and parasitic infections, the functional activities of these cytokines during fungal infections are poorly understood. We examined here the impact of IFN-β on the response of human monocyte-derived dendritic cells (DCs) infected in vitro with Aspergillus fumigatus. Having found that A. fumigatus-infected DCs do not express IFN-β, we evaluated the effect of the exogenous addition of IFN-β on the maturation of human DCs induced by the infection with A. fumigatus conidia. Although the phagocytosis of the fungus was not affected by IFN-β treatment, the expression of CD86 and CD83 induced upon A. fumigatus challenge was enhanced in IFN-β-conditioned DCs, which also showed an increased expression of IL-27 and IL-12p70, members of IL-12 family. Through these modifications, IFN-β improved the capacity of DCs to promote an anti-Aspergillus T helper type 1 response, as evaluated by mixed leucocyte reaction, which plays a crucial role in the control of invasive aspergillosis. Our results identified a novel effect of IFN-β on anti-Aspergillus immune responses which, in turn, might open new perspectives on the use of IFN-β in immunotherapy for fungal infections aimed at enhancing the immunological functions of DCs.
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- 2010
5. Bystander inhibition of dendritic cell differentiation by Mycobacterium tuberculosis ‐induced IL‐10
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Elena Giacomini, Richard Pine, Maria Elena Remoli, Martina Severa, Eliana M. Coccia, Roberto Nisini, Maria Cristina Gagliardi, Elisabetta Iona, Elisa Petruccioli, and Valérie Gafa
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STAT3 Transcription Factor ,CD14 ,p38 mitogen-activated protein kinases ,Immunology ,chemical and pharmacologic phenomena ,Dendritic cell differentiation ,Biology ,p38 Mitogen-Activated Protein Kinases ,Monocytes ,Immune system ,medicine ,Humans ,Tuberculosis ,Immunology and Allergy ,Monocyte ,Interferon-alpha ,Cell Differentiation ,Bystander Effect ,Dendritic Cells ,Mycobacterium tuberculosis ,Cell Biology ,Interleukin-10 ,Cell biology ,Interleukin 10 ,medicine.anatomical_structure ,Culture Media, Conditioned ,STAT protein ,Cytokines ,Tumor necrosis factor alpha ,Signal Transduction - Abstract
Mycobacterium tuberculosis (Mtb) evades the immune response by impairing the functions of different antigen-presenting cells. We have recently shown that Mtb hijacks differentiation of monocytes into dendritic cells (DCs). To further characterize the mechanisms underlying this process, we investigated the consequences of inducing dendritic cell differentiation using interferon-α and granulocyte-macrophage colony-stimulating factor in the presence of supernatants (SNs) obtained from monocyte cultures treated with or without heat-inactivated Mtb. Although the SNs from control cultures do not interfere with the generation of fully differentiated DCs, monocytes stimulated with SNs from Mtb-stimulated cells (SN Mtb) remained CD14(+) and poorly differentiated into CD1a(+) cells. Among cytokines known to affect dendritic cell differentiation, we observed a robust production of interleukin-1β, interleukin-6, interleukin-10 and tumor necrosis factor-α upon Mtb stimulation. However, only interleukin-10 neutralization through the addition of soluble interleukin-10 receptor reversed the inhibitory activity of SN Mtb. Accordingly, the addition of recombinant interleukin-10 was able to significantly reduce CD1a expression. The interaction of Mtb with differentiating monocytes rapidly activates p38 mitogen-activated protein kinase, signal transducer and activator of transcription pathways, which are likely involved in interleukin-10 gene expression. Taken together, our results suggest that Mtb may inhibit the differentiation of bystander non-infected monocytes into DCs through the release of interleukin-10. These results shed light on new aspects of the host-pathogen interaction, which might help to identify innovative immunological strategies to limit Mtb virulence.
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- 2010
6. Characterization of Immunostimulatory CpG-Rich Sequences from DifferentBifidobacteriumSpecies
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Odile Ménard, Nathalie Kapel, Bertrand Rodriguez, Anne-Judith Waligora-Dupriet, Valérie Gafa, and Marie-José Butel
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DNA, Bacterial ,Bifidobacterium longum ,CpG Oligodeoxynucleotide ,In silico ,Genetics and Molecular Biology ,Applied Microbiology and Biotechnology ,Genome ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Humans ,Bifidobacterium ,Genetics ,Base Sequence ,Ecology ,biology ,Tumor Necrosis Factor-alpha ,Toll-Like Receptors ,Infant ,TLR9 ,biology.organism_classification ,CpG site ,chemistry ,CpG Islands ,Dinucleoside Phosphates ,DNA ,Food Science ,Biotechnology - Abstract
The beneficial effects ofBifidobacteriumare partly due to its immunostimulatory properties. These immunostimulatory properties may be linked to the presence of unmethylated CpG motifs specific to bacterial DNA, which may induce a TH1 response by activating Toll-like receptors (TLR). Usingin silicoanalyses, PCR amplification, and dot blotting, we characterized the CpG content of various bifidobacterial strains and evaluated the immunostimulatory properties and genomic heterogeneity of these motifs in the genus. Ourin silicostudy, based on entire genome sequences from five bifidobacterial strains, showed thatBifidobacteriumgenomes contain numerous CpG motifs, including 5′-purine-purine-CG-pyrimidine-pyrimidine-3′ and 5′-purine-TCG-pyrimidine-pyrimidine-3′ motifs, and biologically active sequences previously identified in lactic acid bacteria. We identified four CpG-rich sequences withBifidobacterium longumNCC2705. Two sequences with a percent G+C of about 68% included 14 and 16 CpG motifs. Two sequences with a percent G+C of about 60% included 16 and 6 CpG motifs. These sequences induce the production of monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor alpha (TNF-α) through a pattern of TLR9 stimulation on RAW 264.7 macrophages. No link could be established between their immunostimulatory properties, the number of CpG motifs, and percent G+C. We investigated inter- and intraspecies heterogeneity in 71 strains of various origins. These sequences were highly conserved in the genus. No link was found between the presence of the CpG-rich sequence and the origin of the strains (healthy, allergic, or preterm infants). The high frequency of CpG motifs in the DNA ofBifidobacteriummay play an important role in the immunostimulatory properties of commensal or probiotic bifidobacterial strains.
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- 2010
7. IFN-β modulates the response to TLR stimulation in human DC: Involvement of IFN regulatory factor-1 (IRF-1) in IL-27 gene expression
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Martina Severa, Valérie Gafa, Roberto Lande, Elena Giacomini, Eliana M. Coccia, and Maria Elena Remoli
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Lipopolysaccharides ,Receptors, CCR7 ,Immunology ,Immunoglobulins ,Stimulation ,C-C chemokine receptor type 7 ,Biology ,Antigens, CD ,Humans ,Immunology and Allergy ,Secretion ,Autocrine signalling ,Cells, Cultured ,CD86 ,Membrane Glycoproteins ,Innate immune system ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Interleukins ,Dendritic Cells ,Interferon-beta ,Acquired immune system ,Interleukin-12 ,Toll-Like Receptor 2 ,Interleukin-10 ,Toll-Like Receptor 4 ,Protein Subunits ,TLR2 ,Gene Expression Regulation ,B7-2 Antigen ,Interferon Regulatory Factor-1 ,Signal Transduction - Abstract
Type I IFN are cytokines which play a central role in host resistance to viral or microbial infections and are important components linking innate and adaptive immunity. We and others have previously demonstrated that the production of IFN-beta by DC following bacterial infections or TLR triggering influences, in an autocrine manner, their maturation. In this study, we investigated whether IFN-beta release modulates the phenotype of the immature DC and their response to a subsequent TLR stimulation. The induction of CD86, HLA-DR, CD38 and B7H1 and the absence of CCR7 and CD83 expression upon IFN-beta treatment suggest that IFN-beta-primed DC remain at the site of infection acquiring an activated phenotype. These results prompted us to investigate the response of IFN-beta-primed DC to TLR stimulation. While IFN-beta pretreatment increases slightly the expression of maturation markers in TLR2- or TLR4-stimulated DC, it is able to modulate selectively the secretion of inflammatory and immuno-regulating cytokines. Interestingly, IL-27p28 subunit was induced by IFN-beta alone or during LPS-induced maturation of DC in a type I IFN-dependent manner through IFN regulatory factor-1 (IRF-1) activation. Taken together, our results shed light on the capacity of IFN-beta to finely tune DC response to invading pathogens.
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- 2007
8. IFN-β Therapy Regulates TLR7-Mediated Response in Plasmacytoid Dendritic Cells of Multiple Sclerosis Patients Influencing an Anti-Inflammatory Status
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Viviana Annibali, Martina Severa, Marco Salvetti, Fabiana Rizzo, Eliana M. Coccia, Maria Chiara Buscarinu, Arianna Fornasiero, Elena Giacomini, Valérie Gafa, and Silvia Romano
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Adult ,Male ,Interleukin-27 ,Multiple Sclerosis ,autoimmune-diseases ,interferon-beta ,th17 cells ,impaired maturation ,immune regulation ,alpha production ,viral-infection ,t-cells ,b-cell ,expression ,medicine.medical_treatment ,Immunology ,Anti-Inflammatory Agents ,Inflammation ,Biology ,Peripheral blood mononuclear cell ,Interleukin-23 ,Virology ,Interleukin 23 ,medicine ,Humans ,Immunologic Factors ,Interleukin 27 ,Multiple sclerosis ,Interferon-alpha ,hemic and immune systems ,Cell Differentiation ,Cell Biology ,TLR7 ,Dendritic Cells ,Middle Aged ,medicine.disease ,Interleukin-10 ,Interleukin 10 ,Cytokine ,Toll-Like Receptor 7 ,Leukocytes, Mononuclear ,Female ,medicine.symptom - Abstract
Plasmacytoid dendritic cells (pDCs) display altered immune-phenotype in multiple sclerosis (MS) patients and are found actively recruited in postmortem MS brain lesions, implying that their immune regulation may represent an important aspect of MS pathogenesis. Because of the reported Toll-like receptor 7 (TLR7) implication in autoimmunity, in this study we characterized how IFN-β therapy impacts on pDC activation to TLR7 triggering in MS patients, aspect only poorly investigated so far. In vivo IFN-β administration regulates pDC functions in TLR7-treated peripheral blood mononuclear cell (PBMC) cultures differently from what is observed in isolated cells, suggesting that IFN-β may activate inhibitory mechanisms in MS peripheral blood involved in turning off pDC response to dampen the ongoing inflammation. Indeed, IL-10, a key regulatory cytokine found increased upon TLR7 stimulation in in vivo IFN-β-exposed PBMCs, directly reduced pDC-mediated IFN-α production. IFN-β therapy also shaped T-cell responses by decreasing TLR7-induced pDC maturation and inducing T-cell inhibitory molecules. Accordingly, raised pDC-induced IL-27 and decreased IL-23 expression, together with high IL-10 level, contribute to inhibit Th17 cell differentiation. Our study uncovered a role for IFN-β in the regulation of TLR7-mediated pDC responses in MS toward an anti-inflammatory phenotype opening new opportunities to better understand mechanisms of action of this drug in controlling MS immunopathogenesis.
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- 2015
9. Human Dendritic Cells followingAspergillus fumigatusInfection Express the CCR7 Receptor and a Differential Pattern of Interleukin-12 (IL-12), IL-23, and IL-27 Cytokines, Which Lead to a Th1 Response
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Maria Cristina Gagliardi, Valérie Gafa, Martina Severa, Roberto Lande, Roberto Nisini, Paolo Di Francesco, Eliana M. Coccia, Maria Elena Remoli, Delphine Aldebert, Renée Grillot, Carlo Ramoni, and Elena Giacomini
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Receptors, CCR7 ,medicine.medical_treatment ,Immunology ,Lymphocyte Activation ,Interleukin-23 ,Microbiology ,Aspergillus fumigatus ,Proinflammatory cytokine ,Immune system ,medicine ,Aspergillosis ,Humans ,Macrophage ,Cells, Cultured ,Innate immune system ,biology ,Interleukins ,Interleukin-17 ,Cell Differentiation ,Dendritic Cells ,Dendritic cell ,Th1 Cells ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,biology.organism_classification ,Interleukin-12 ,Infectious Diseases ,Cytokine ,Interleukin-23 Subunit p19 ,Interleukin 12 ,Cytokines ,Receptors, Chemokine ,Parasitology ,Fungal and Parasitic Infections - Abstract
Aspergillus fumigatus is a saprophytic fungus responsible for approximately 90% of human cases of aspergillosis. It causes a usually fatal invasive aspergillosis (IA) in immunocompromised hosts (13). The airborne conidia of A. fumigatus present in the atmosphere are small enough (2 to 3 μm in diameter) to be continuously inhaled and to reach the human lung alveoli, where they are captured, ingested, and killed by resident phagocytes in immunocompetent individuals (20). Otherwise, in immunocompromised patients, the conidia can overcome the immune defense mechanisms, germinating into mycelia that invade the lung. The major recognized risk factors for IA are defects in phagocytic function (25), corticosteroid-induced suppression of macrophage conidiocidal activity (30, 43), and long-lasting neutropenia (15). Numerous studies have shown that innate immune mechanisms play a key role in the defense against A. fumigatus. In particular, alveolar macrophages and neutrophils are the main cells involved in the rapid killing of A. fumigatus through oxidative and nonoxidative mechanisms (33, 50). Although the importance of the innate response has been well described both in vitro and in vivo, a recent observation showed that healthy individuals or patients with clinical evidence of IA and disease regression in antifungal therapy featured positive lymphoproliferation and a high level of gamma interferon (IFN-γ) (19). Correlated to these results, studies with the murine model of IA showed that resistance to infection was associated with the production of IFN-γ, tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12), whereas a dominant release of Th2 cytokines by interstitial lung lymphocytes was correlated with the development of disease (8, 9). The fact that the Th response may modify the outcome of IA indirectly indicates a key role for human dendritic cells (DC) in the modulation of the immune response against A. fumigatus. Indeed, at the site of primary infection, DC constitute an integral part of the innate immune system, recognizing the pathogen and secreting inflammatory cytokines, such as TNF-α, IL-6, and IL-1 (38). After interacting with the pathogen, DC mature and migrate into the lymphoid organs, where they interact with T cells, transmitting information on the type of infection encountered and inducing a T-cell response through a coordinated stimulation via T-cell receptor engagement, costimulatory molecules, and cytokine production (37). IL-12p70, type I IFN, and IL-18 are well-documented examples of Th1-promoting cytokines (12). Recently other factors, belonging to the IL-12 family, were reported to play a key role in promoting a Th1 response. In particular, IL-23 acts primarily on effector T cells, prolonging and sustaining their IFN-γ production (46) and stimulating the proliferation of memory T cells (27, 52), whereas IL-27 has a strong effect, especially on naive Th cells inducing the early production of IFN-γ (32). The interaction of human DC with A. fumigatus and its consequence for the immune defense against this pathogen have been studied previously (4, 18, 41, 44). However in the present study, we investigated the impact of A. fumigatus infection on human DC maturation, focusing on the expression of CCR7 and novel members of the IL-12 family. Interestingly, we observed that the majority of DC underwent full maturation, although CCR7 expression was observed only in DC that had internalized the conidia. In addition, analysis of inflammatory and immunoregulatory cytokines was performed in order to determine the capacity of DC to elicit an anti-Aspergillus immune response. In particular, our results with regard to the IL-12, IL-23, and IL-27 expression profiles provide new insights into the mechanisms promoting the anti-Aspergillus Th1 response.
- Published
- 2006
10. Human cytomegalovirus downregulates complement receptors (CR3, CR4) and decreases phagocytosis by macrophages
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Alexandrine Pastor, Olivier Manches, Emmanuel Drouet, Valérie Gafa, Delphine Aldebert, Renée Grillot, and Pierre Ambroise-Thomas
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Human cytomegalovirus ,Opportunistic infection ,viruses ,Cytomegalovirus ,Integrin alphaXbeta2 ,Macrophage-1 Antigen ,Complement receptor ,Biology ,Cell Line ,Microbiology ,Immune system ,Phagocytosis ,Virology ,Candida albicans ,parasitic diseases ,medicine ,Humans ,Macrophage ,Innate immune system ,Macrophages ,Monocyte ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,Immunity, Innate ,Infectious Diseases ,medicine.anatomical_structure ,Gene Expression Regulation ,Immunology - Abstract
Human cytomegalovirus (HCMV) infection is associated with an increased susceptibility to opportunistic infections. Although the subversion of adaptive immune responses has been extensively studied, the consequences of HCMV infection on natural immune responses are not well documented. A striking selective downmodulation of CD11b/CD18 (CR3) or CD11c/CD18 (CR4) was found upon HCMV infection, on two models, the monocytic THP-1 cell line and monocyte- derived macrophages. HCMV-infected macrophages have an altered adhesion/phagocytic capacity to Candida albicans, a pathogen responsible for some opportunistic infections in immunocompromised patients. These results suggest a new mechanism implicated in the augmentation of opportunistic infections in HCMV patients. J. Med. Virol. 76:361–366, 2005. © 2005 Wiley-Liss, Inc.
- Published
- 2005
11. Etoposide encapsulation in surface-modified poly(lactide-co-glycolide) nanoparticles strongly enhances glioma antitumor efficiency
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Sylvain Dukic, Maité Callewaert, Laurence Van Gulick, V. Gaëlle Roullin, Mélanie Vittier, Michael Molinari, Valérie Gafa, and Marie-Christine Andry
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Materials science ,Cell Survival ,Surface Properties ,Biomedical Engineering ,Nanoparticle ,Poloxamer ,Pharmacology ,Monocytes ,Biomaterials ,chemistry.chemical_compound ,Mice ,Polylactic Acid-Polyglycolic Acid Copolymer ,Glioma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Lactic Acid ,Particle Size ,Etoposide ,Cells, Cultured ,Drug Carriers ,biology ,Brain Neoplasms ,Topoisomerase ,Metals and Alloys ,Brain ,medicine.disease ,Antineoplastic Agents, Phytogenic ,In vitro ,Bioavailability ,PLGA ,chemistry ,Cell culture ,Ceramics and Composites ,biology.protein ,Nanoparticles ,Polyglycolic Acid ,medicine.drug - Abstract
Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting Topoisomerase II, commonly used in pediatric brain chemotherapeutic schemes as mildly toxic. Unfortunately, despite its appropriate solubilization in vehicle solvents, its poor bioavailability and limited passage of the blood–brain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva®) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110–130 nm) using a fully biocompatible nanoprecipitation technique. The presence of coprecipitated P188 on encapsulation efficacies and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Inflammatory response was checked by FACS analysis on human monocytes. Cytotoxic activity of the various simple (Teva®) or double (Teva®-loaded NPs) formulations was studied on the murine C6 and F98 cell lines. Obtained results suggest that, although noninflammatory neither nontoxic by themselves, the use of PLGA and PLGA/P188 nanoencapsulations over pre-existing etoposide formulation could induce a greatly improved cytotoxic activity. This approach demonstrated a promising perspective for parenteral delivery of VP16 and potential development of a therapeutic entity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
- Published
- 2012
12. ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells
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Marco Corazzari, Maria Elena Remoli, Roland Brosch, Laura Falasca, Giovanni Delogu, Roxane Simeone, Alessandra Romagnoli, Eliana M. Coccia, Delia Goletti, Valérie Gafa, Gian Maria Fimia, Mauro Piacentini, Elena Giacomini, Manuela Pardini, Marilena P. Etna, National Institute for Infectious Diseases 'Lazzaro Spallanzani', Istituto Superiore di Sanità (ISS), Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris] (IP), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Università degli Studi di Roma Tor Vergata [Roma], The study was supported by grants from Ministry for Health of Italy: 'Ricerca Corrente' to M.P. G.M.F. and D.G., 'Ricerca Finalizzata' RF06.76.1, RF-IMI-2009-1302952 to D.G., RF07.103 to E.M.C., G.M.F. and D.G., by grants from the FP7 program of the European Community n°241745 to R.B. and E.M.C., n°40H58 to D.G. and APO-SYS Health F4-2007-200767 to M.P., European Project: 241745,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,NEWTBVAC(2010), Istituto Superiore di Sanita [Rome], Institut Pasteur [Paris], Università cattolica del Sacro Cuore [Roma] (Unicatt), Romagnoli, Alessandra, Etna, Marilena P, Giacomini, Elena, Pardini, Manuela, Remoli, Maria Elena, Corazzari, Marco, Falasca, Laura, Goletti, Delia, Gafa, Valérie, Simeone, Roxane, Delogu, Giovanni, Piacentini, Mauro, Brosch, Roland, Fimia, Gian Maria, and Coccia, Eliana M.
- Subjects
MESH: Mycobacterium bovis ,MESH: Mycobacterium tuberculosis ,Autophagosome maturation ,[SDV]Life Sciences [q-bio] ,Mycobacterium tuberculosi ,vaccine ,Phagosomes ,Sirolimu ,BCG ,MESH: Tuberculosis ,MESH: Bacterial Secretion Systems ,Bacterial Secretion Systems ,Phagosome ,Cells, Cultured ,Mycobacterium bovis ,Cultured ,biology ,MESH: Dendritic Cells ,Effector ,Cell Differentiation ,respiratory system ,Basic Research Paper ,3. Good health ,Th1 Cell ,Biological Markers ,Human ,MESH: Cells, Cultured ,MESH: Cell Differentiation ,Settore BIO/06 ,Cells ,Dendritic Cells ,Humans ,Mycobacterium tuberculosis ,Sirolimus ,Th1 Cells ,Tuberculosis ,Autophagy ,Tuberculosi ,Dendritic Cell ,complex mixtures ,Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA ,Microbiology ,Immune system ,MESH: Phagosomes ,Mycobacterium bovi ,MESH: Autophagy ,Secretion ,Molecular Biology ,MESH: Humans ,RD1 region ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,bacterial infections and mycoses ,MESH: Th1 Cells ,Biological Marker ,MESH: Biomarkers ,bacteria ,MESH: Sirolimus ,ESX1/type VII secretion system ,Biomarkers - Abstract
International audience; Emerging evidence points to an important role of autophagy in the immune response mediated by dendritic cells (DC) against Mycobacterium tuberculosis (Mtb). Since current vaccination based on Bacillus Calmette-Guerin (BCG) is unable to stop the tuberculosis epidemic, a deeper comprehension of the alterations induced by Mtb in DC is essential for setting new vaccine strategies. Here, we compared the capacity of virulent (H37Rv) and avirulent (H37Ra) Mtb strains as well as BCG to modulate autophagy in human primary DC. We found that Mtb H37Rv impairs autophagy at the step of autophagosome-lysosome fusion. In contrast, neither Mtb H37Ra nor BCG strains were able to hamper autophagosome maturation. Both these attenuated strains have a functional inhibition of the 6kD early secreted antigenic target ESAT-6, an effector protein of the ESAT-6 Secretion System-1(ESX-1)/type VII secretion system. Notably, the ability to inhibit autophagy was fully restored in recombinant BCG and Mtb H37Ra strains in which ESAT-6 secretion was re-established by genetic complementation using either the ESX-1 region from Mtb (BCG::ESX-1) or the PhoP gene (Mtb H37Ra::PhoP), a regulator of ESAT-6 secretion. Importantly, the autophagic block induced by Mtb was overcome by rapamycin treatment leading to an increased interleukin-12 expression and, in turn, to an enhanced capacity to expand a Th1-oriented response. Collectively, our study demonstrated that Mtb alters the autophagic machinery through the ESX-1 system, and thereby opens new exciting perspectives to better understand the relationship between Mtb virulence and its ability to escape the DC-mediated immune response.
- Published
- 2012
13. CS16-6. Plasmacytoid Dendritic Cells are infected by Epstein Barr virus and induces TLR- dependent type I IFN production
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Marco Corazzari, Eliana M. Coccia, Valérie Gafa, Regina Feederle, Elena Giacomini, Alessandra Romagnoli, Gian Maria Fimia, Pankaj Trivedi, Fabiana Rizzo, Henri Jacques Delecluse, Eleni Anastasiadou, and Martina Severa
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Immunology ,medicine ,Immunology and Allergy ,Hematology ,Biology ,medicine.disease_cause ,Molecular Biology ,Biochemistry ,Epstein–Barr virus ,Virology - Published
- 2011
14. Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis
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Eliana M. Coccia, Manuela Pardini, Valérie Gafa, Marta Scandurra, Maria Elena Remoli, Elena Giacomini, and Lanfranco Fattorini
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MAPK/ERK pathway ,lcsh:Immunologic diseases. Allergy ,Article Subject ,MAP Kinase Signaling System ,Immunology ,Cell Culture Techniques ,Gene Expression ,Monocytes ,Proinflammatory cytokine ,Mycobacterium tuberculosis ,chemistry.chemical_compound ,Gene expression ,Immunology and Allergy ,Humans ,Phosphorylation ,Transcription factor ,Th1-Th2 Balance ,biology ,NF-kappa B ,NF-κB ,General Medicine ,NFKB1 ,biology.organism_classification ,chemistry ,Cytokines ,Interferon Regulatory Factor-3 ,Signal transduction ,lcsh:RC581-607 ,Research Article ,Signal Transduction - Abstract
Knowledge of the molecular events regulating the innate response toMycobacterium tuberculosis(Mtb) is critical for understanding immunological pathogenesis and protection from tuberculosis. To this aim, the regulation and the expression of regulatory and proinflammatory cytokines were investigated in human primary monocytes upon Mtb infection. We found that Mtb-infected monocytes preferentially express a proinflammatory cytokine profile, including IL-6, TNF-α, and IL-1β. Conversely, among the regulatory cytokines, Mtb elicited IL-10 and IL-23 release while no expression of IL-12p70, IL-27, and IFN-βwas observed. The analysis of the signalling pathways leading to this selective cytokine expression showed that in monocytes Mtb activates MAPK and NF-κB but is unable to stimulate IRF-3 phosphorylation, a transcription factor required for IL-12p35 and IFN-βgene expression. Thus, by inducing a specific cytokine profile, Mtb can influence the immunoregulatory properties of monocytes, which represent important target of novel vaccinal strategies against Mtb infection.
- Published
- 2010
15. Epstein-Barr virus and plasmacytoid dendritic cells: A possible duet in autoimmunity
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Eleni Anastasiadou, Valérie Gafa, Martina Severa, Francesca Aloisi, Eliana M. Coccia, Pankaj Trivedi, Barbara Serafini, and Elena Giacomini
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Immunology ,medicine ,Immunology and Allergy ,Hematology ,Biology ,medicine.disease_cause ,Molecular Biology ,Biochemistry ,Epstein–Barr virus ,Virology ,Autoimmunity - Published
- 2009
16. IFN-beta improves BCG immunogenicity by acting on DC maturation
- Author
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Maria Elena Remoli, Eliana M. Coccia, Valérie Gafa, Manuela Pardini, Lanfranco Fattorini, and Elena Giacomini
- Subjects
medicine.medical_treatment ,Immunology ,Mycobacterium tuberculosis ,Immune system ,medicine ,Immunology and Allergy ,Humans ,Tuberculosis Vaccines ,Mycobacterium bovis ,biology ,Immunogenicity ,Cell Biology ,Dendritic Cells ,Interferon-beta ,Th1 Cells ,Extracellular Mediators and Effector Molecules ,biology.organism_classification ,Interleukin-12 ,Cytokine ,Interleukin 12 ,BCG Vaccine ,Tuberculosis vaccines ,BCG vaccine - Abstract
Given the variable protective efficacy provided by Mycobacterium bovis bacillus Calmette-Guérin (BCG), there is an urgent need to develop new vaccines against tuberculosis. As dendritic cells (DC) play a critical role in initiating and regulating a protective T cell response against the pathogens, the comprehension of mycobacterium-induced modulation of DC functions is critical to pinpoint new, immunological strategies. To this end, a comparative analysis of the effect induced by BCG and Mycobacterium tuberculosis (Mtb) infection on the DC immunophenotype indicated that BCG is less efficient in inducing DC maturation than Mtb. In addition, BCG-infected DC poorly expressed IFN-β and displayed a reduced production of IL-12 as compared with Mtb-stimulated cells. The impaired expression of IL-12p35 and IFN-β is likely a result of the inability of BCG to induce the activation of the IFN regulatory factor-3. Taking into account these data, we sought to investigate whether the exogenous addition of IFN-β, a cytokine that exerts important effects on the immune system, could enhance the Th1-polarizing capacity of BCG-infected DC. Interestingly, when DC infected by BCG were pretreated in vitro with IFN-β, they displayed a fully mature phenotype and released a significant amount of bioactive IL-12p70, which resulted in an enhanced Th1 response. This study demonstrates that IFN-β potentiates DC immunological functions following BCG infection, thus suggesting IFN-β as a possible candidate as vaccine adjuvant.
- Published
- 2008
17. Evidence for intestinal heterogenic expression of di-tripeptides transporter PepT1 during experimental cryptosporidiosis in neonatal rats
- Author
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Perrine Marquet, Leila Snouber-Choucha, Bruno Saubaméa, Nathalie Kapel, Valérie Gafa, and Laurence Barbot-Trystram
- Subjects
Pathology ,medicine.medical_specialty ,Cryptosporidiosis ,Biology ,law.invention ,Confocal microscopy ,law ,medicine ,Parasite hosting ,Animals ,Intestinal Mucosa ,Cryptosporidium parvum ,Microscopy, Confocal ,General Veterinary ,Peptide transporter 1 ,Membrane Transport Proteins ,Transporter ,General Medicine ,Subcellular localization ,biology.organism_classification ,Molecular biology ,Small intestine ,Actins ,Staining ,Rats ,Infectious Diseases ,medicine.anatomical_structure ,Animals, Newborn ,Insect Science ,biology.protein ,Microscopy, Electron, Scanning ,Parasitology ,Female - Abstract
Cryptosporidium parvum is a protozoan parasite that causes intestinal malabsorptive syndrome and malnutrition. Considering the importance of di-tripeptide absorption for nutritional status, we previously investigated the regulation of PepT1 transporter in the suckling rat model of acute cryptosporidiosis and showed that PepT1 protein expression and activity were not modified in the parasitized intestine. Here we used confocal microscopy performed on intestinal villi to determine the subcellular localization of PepT1 together with f-actin and parasites. For this purpose, confocal microscopy using vibratome thick sections was developed on the distal small intestine, the preferential site of parasite implantation. Results showed major heterogeneity of apical PepT1 expression among enterocytes, which did not correlate with actin staining or parasite implantation. These results underscore the importance of considering the effect of C. parvum at the cellular scale and not only in the entire epithelium.
- Published
- 2008
18. Plasmacytoid dendritic cells in multiple sclerosis: intracerebral recruitment and impaired maturation in response to interferon-beta
- Author
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Eliana M. Coccia, Elena Giacomini, Valérie Gafa, Barbara Serafini, Roberto Lande, Giovanni Ristori, Martina Severa, Maria Elena Remoli, Marc Parmentier, Andrea Visconti, Francesca Aloisi, and Marco Salvetti
- Subjects
Adult ,Male ,Myxovirus Resistance Proteins ,Multiple Sclerosis ,medicine.medical_treatment ,Lymphocyte ,CD3 ,Plasma Cells ,Lymphocyte Activation ,Nerve Fibers, Myelinated ,B7-H1 Antigen ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,Cellular and Molecular Neuroscience ,Antigen ,Antigens, CD ,GTP-Binding Proteins ,Interferon ,medicine ,Humans ,Immunologic Factors ,Lymphocytes ,Cerebral Cortex ,CD86 ,biology ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,Interferon-beta ,General Medicine ,Dendritic cell ,Middle Aged ,Chemotaxis, Leukocyte ,Phenotype ,Cytokine ,medicine.anatomical_structure ,Neurology ,Immunology ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Female ,Neurology (clinical) ,Chemokines ,Biomarkers ,medicine.drug - Abstract
The roles of plasmacytoid dendritic cells (pDCs) and their response to interferon (IFN)-beta therapy in multiple sclerosis (MS) patients are poorly understood. We identified pDC accumulation in white matter lesions and leptomeninges of MS brains and abundant expression of the Type I IFN-induced protein MxA, mainly in perivascular CD3+ lymphocytes in lesions, indicating Type I IFN production by activated pDCs. The pDC chemoattractant chemerin was detected in intralesional cerebrovascular endothelial cells, and the chemerin receptor was expressed on infiltrating leukocytes, including pDCs. The effect of IFN-beta on pDC phenotype and function was evaluated in MS patients before and during IFN-beta treatment. Although IFN-beta did not modify the frequency and immature phenotype of circulating pDC, they showed lower expression of major histocompatibility complex Class II and blood-dendritic cell antigen 2 molecules and upregulation of CD38 and B7H1 costimulatory molecules. On exposure to CpG (a site where cytosine [C] lies next to guanine [G] in the DNA sequence [the p indicates that C and G are connected by a phosphodiester bond]) oligodeoxynucleotides in vitro, pDCs from IFN-beta-treated MS patients showed reduced expression of the pDC maturation markers CD83 and CD86 molecules; in vitro IFN-beta treatment of pDCs from healthy donors resulted in lower secretion of proinflammatory cytokines, including IFN-alpha, and a decreased ability to stimulate allogeneic T cells in response to maturative stimuli. These data indicate that IFN-beta modulates the immunologic functions of pDC, thus identifying pDCs as a novel target of IFN-beta therapy in MS patients.
- Published
- 2008
19. Sensitization to TLR7 agonist in IFN-beta-preactivated dendritic cells
- Author
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Elena Giacomini, Valérie Gafa, Martina Severa, Maria Elena Remoli, Viviana Annibali, Marco Salvetti, Roberto Lande, Eliana M. Coccia, and Mark A. Tomai
- Subjects
Lipopolysaccharides ,Immunology ,Priming (immunology) ,Biology ,CD38 ,Ligands ,Proinflammatory cytokine ,Transcriptome ,Immune system ,Humans ,Immunology and Allergy ,Cells, Cultured ,CD86 ,Gene Expression Profiling ,Cell Differentiation ,Dendritic Cells ,Interferon-beta ,TLR7 ,TLR8 ,Immunity, Innate ,Cell biology ,Toll-Like Receptor 7 ,Antigens, Surface ,Cytokines ,Inflammation Mediators ,Interferon Regulatory Factor-1 - Abstract
TLRs interact with a growing list of pathogen-derived products and these interactions drive the activation of innate and adaptive immune responses. Dendritic cells (DC) play a key role in these events expressing a heterogeneous repertoire of TLRs. We have previously demonstrated the production of type I IFNs in DC following bacterial infections and TLR triggering. In this study, we sought to characterize the transcriptome specifically induced in human DC by IFN-β production stimulated upon LPS treatment. To this aim, by using cDNA microarrays, we compared the transcriptome of DC following LPS treatment in the absence or presence of neutralizing anti-type I IFN Abs. Interestingly, we found that the expression of TLR7 was induced during LPS-induced maturation of DC in a type I IFN-dependent manner. The induction of TLR7 in maturing DC was mainly a consequence of the transcriptional activity of IRF-1, whose binding site was located within TLR7 promoter. Moreover, we also demonstrated that “priming” of immature DC, that usually express TLR8 but not TLR7, with exogenous IFN-β induced a functionally active TLR7. In fact, treatment with the TLR7-specific ligand 3M-001 up-regulated the expression of CD83, CD86, and CD38 in IFN-β-primed DC but not in immature DC. Therefore, a robust enhancement in proinflammatory as well as regulatory cytokines was observed. These data suggest that TLR4-mediated type I IFN release activates specific transcription programs in DC amplifying the expression of pathogen sensors to correctly and combinatorially respond to a bacterial as well as viral infection.
- Published
- 2007
20. NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation
- Author
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Maria Elena Remoli, Eliana M. Coccia, Elena Giacomini, Valérie Gafa, Roberto Lande, Sandra Pellegrini, Josiane Ragimbeau, Martina Severa, Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Infectious, Parasitic and Immune-Mediated Diseases [Rome], Istituto Superiore di Sanità (ISS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Istituto Superiore di Sanita [Rome]
- Subjects
Lipopolysaccharides ,Immunology ,Molecular Sequence Data ,Repressor ,Biology ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Gene expression ,Immunology and Allergy ,Humans ,Binding site ,10. No inequality ,Promoter Regions, Genetic ,Transcription factor ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Binding Sites ,Base Sequence ,NF-kappa B ,NF-κB ,Cell Differentiation ,Cell Biology ,Dendritic cell ,Dendritic Cells ,STAT4 Transcription Factor ,Molecular biology ,Transcription Factor AP-1 ,chemistry ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Chromatin immunoprecipitation ,030215 immunology - Abstract
The transcription factor STAT-4 plays a pivotal role in the IL-12-mediated development of naive CD4+ T cells into the Th1 phenotype. Initially thought to be restricted to the lymphoid lineage, STAT-4 was subsequently shown to be expressed in the myeloid compartment, mainly in activated monocytes, macrophages, and dendritic cells (DC). Here, we have studied STAT-4 in human monocyte-derived DC, and we demonstrated that its expression can be induced by multiple stimuli, such as the ligands for TLR-4, TLR-2, and TLR-3, different pathogens, CD40 ligand, and the proinflammatory cytokines TNF-α and IL-1β. It is interesting that we found that STAT-4 is tyrosine-phosphorylated in response to type I IFN but not IL-12 in human mature DC. Cloning and functional analysis of the STAT-4 promoter showed that a NF-κB binding site, localized at –969/–959 bp upstream of the transcriptional start site, is involved in the regulation of this gene in primary human DC. EMSAs using a probe containing this NF-κB binding sequence and chromatin immunoprecipitation indicated that p65/p50 and p50/p50 dimers were the main NF-κB/Rel proteins involved in STAT-4 gene expression in maturing DC. The mutation of this κB site or the overexpression of the repressor IκBα exerted an inhibitory effect on a STAT-4 promoter-driven reporter as well as on STAT-4 expression. Altogether, these results indicate that STAT-4 can be finely tuned along with DC maturation through NF-κB activation and that its induction may be involved in preparing the DC to be receptive to the cytokine environment present in lymphoid organs.
- Published
- 2007
21. In vitro infection of human dendritic cells by Aspergillus fumigatus conidia triggers the secretion of chemokines for neutrophil and Th1 lymphocyte recruitment
- Author
-
Maria Cristina Gagliardi, Elena Giacomini, Valérie Gafa, Maria Elena Remoli, Martina Severa, Renée Grillot, Roberto Lande, and Eliana M. Coccia
- Subjects
Chemokine ,Lymphocyte ,Immunology ,Lymphocyte Activation ,Microbiology ,Aspergillus fumigatus ,Immune system ,medicine ,Aspergillosis ,Humans ,skin and connective tissue diseases ,Chemokine CCL20 ,biology ,CCL19 ,Interleukin-8 ,hemic and immune systems ,Dendritic cell ,Dendritic Cells ,Macrophage Inflammatory Proteins ,Th1 Cells ,biology.organism_classification ,Acquired immune system ,Chemotaxis, Leukocyte ,Infectious Diseases ,medicine.anatomical_structure ,Neutrophil Infiltration ,Chemokines, CC ,biology.protein ,Chemokine CCL19 ,Chemokines ,Homing (hematopoietic) - Abstract
Given the role played by chemokines in the selective homing of immune cells, we sought to characterize the profile of chemokines produced by human dendritic cells (DC) following in vitro Aspergillus fumigatus infection and their ability to recruit cells involved in the antifungal defense. At the onset of A. fumigatus infection, DC released elevated amounts of CXCL8 that promote the migration of polymorphonuclear cells (PMN). Moreover, soluble factors released from A. fumigatus-infected DC increased also the surface expression of two activation markers, CD11b and CD18, on PMN. A. fumigatus infection resulted also in CCL3, CCL4, CXCL10 and CCL20 productions that induce the migration of effector memory Th1 cells. Moreover, the late expression of CCL19 suggests that A. fumigatus-infected DC could be implicated in the migration of CCR7+ naive T cells and mature DC in lymph nodes. Together these results suggested the involvement of human DC in the regulation of innate and adaptive immunity against A. fumigatus through the recruitment of cells active in the fungal destruction.
- Published
- 2006
22. Intracellular oxidative response of human monocytes and granulocytes to different strains of Aspergillus fumigatus
- Author
-
Valérie Gafa, Delphine Aldebert, Jean Boutonnat, Pierre Ambroise-Thomas, Renée Grillot, and Alexandrine Pastor
- Subjects
Virulence ,Dermatology ,Oxidative phosphorylation ,Fungus ,Aspergillosis ,Monocytes ,Aspergillus fumigatus ,Microbiology ,medicine ,Humans ,skin and connective tissue diseases ,chemistry.chemical_classification ,Reactive oxygen species ,Aspergillus ,Phagocytes ,biology ,Pigmentation ,Rhodamines ,General Medicine ,Spores, Fungal ,biology.organism_classification ,medicine.disease ,Flow Cytometry ,Infectious Diseases ,chemistry ,Immunology ,Reactive Oxygen Species ,Intracellular ,Granulocytes - Abstract
Summary Aspergillus fumigatus is one of the most prevalent airborne fungal pathogens, causing severe and often fatal infections. Its fungal virulence factors have not been clearly identified. Reactive oxygen species produced by phagocytic cells are potent fungicides for A. fumigatus. The aim of this study was to examine the influence of conidia pigmentation, fungal development stage and genotype strain on human leucocytes oxidative response. Various A. fumigatus strains were used and the oxidative response was analysed by flow cytometry. A significant difference was observed between live- and killed-conidia. A pigmentless strain gave an important intracellular oxidative response compared with pigmented strains. But no difference was observed between strains isolated from patients with invasive aspergillosis (IA) and bronchial colonisation. The modification of healthy phagocytes’ oxidative response caused by A. fumigatus components is not sufficient to explain the virulence of fungus and to predict an evolution of patients with IA.
- Published
- 2006
23. Mycobacterium tuberculosis induces a bystander effect on DC differentiation through the release of IL-10
- Author
-
Maria Cristina Gagliardi, Elena Giacomini, Maria Elena Remoli, Martina Severa, Richard Pine, Elisabetta Iona, Elisa Petruccioli, Eliana M. Coccia, Robero Nisini, and Valérie Gafa
- Subjects
biology ,business.industry ,Immunology ,Hematology ,biology.organism_classification ,Biochemistry ,Mycobacterium tuberculosis ,Interleukin 10 ,Bystander effect ,Immunology and Allergy ,Medicine ,business ,Molecular Biology - Published
- 2009
24. PS1-009. TLR responsiveness of B cells is modulated in patients with multiple sclerosis following IFN-β therapy
- Author
-
Valérie Gafa, Maria Elena Remoli, Severa M. Giacomini Elena, Eliana M. Coccia, Rosella Mechelli, Marco Salvetti, Silvia Romano, and Fabiana Rizzo
- Subjects
business.industry ,Multiple sclerosis ,Immunology ,medicine ,Immunology and Allergy ,In patient ,Hematology ,medicine.disease ,business ,Molecular Biology ,Biochemistry - Published
- 2011
25. PS1-036. Mycobacterium tuberculosis ESX-1 secretion system is involved in the control of human dendritic cells maturation
- Author
-
Marco Tilotta, Valérie Gafa, Roland Brosch, Manuela Pardini, Daria Bottai, Maria Elena Remoli, Elena Giacomini, Eliana M. Coccia, and Marilena P. Etna
- Subjects
Mycobacterium tuberculosis ,Immunology ,Immunology and Allergy ,Secretion ,Hematology ,Biology ,biology.organism_classification ,Molecular Biology ,Biochemistry ,Microbiology - Published
- 2011
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