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Dive into the research topics where Elena Ortona is active.

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Featured researches published by Elena Ortona.


Infection and Immunity | 2007

Echinococcus granulosus Antigen B Impairs Human Dendritic Cell Differentiation and Polarizes Immature Dendritic Cell Maturation towards a Th2 Cell Response

Rachele Riganò; Brigitta Buttari; Elisabetta Profumo; Elena Ortona; Federica Delunardo; Paola Margutti; Vincenzo Mattei; Antonella Teggi; Maurizio Sorice; Alessandra Siracusano

ABSTRACT Despite inducing a strong host cellular and humoral immune response, the helminth Echinococcus granulosus is a highly successful parasite that develops, progresses, and ultimately causes chronic disease. Although surgery remains the preferred therapeutic option, pharmacological research now envisages antihelminthic strategies. To understand the mechanisms that E. granulosus uses to escape host immunosurveillance and promote chronic infection, we investigated how two hydatid cyst components, purified antigen B (AgB) and sheep hydatid fluid (SHF), act on host dendritic cell (DC) differentiation from monocyte precursors and how they influence maturation of DC that have already differentiated. We evaluated the immunomodulatory potential of these antigens by performing immunochemical and cytofluorimetric analyses of monocyte-derived DCs from healthy human donors. During monocyte differentiation, AgB and SHF downmodulated CD1a expression and upregulated CD86 expression. Compared with immature DCs differentiated in medium alone (iDCs), AgB- and SHF-differentiated cells stimulated with lipopolysaccharide included a significantly lower percentage of CD83+ cells (P < 10−4) and had weaker costimulatory molecule expression. When stimulated with AgB and SHF, iDCs matured and primed lymphocytes towards the Th2 response typical of E. granulosus infection. SHF and particularly AgB reduced the production of interleukin-12p70 (IL-12p70) and tumor necrosis factor alpha in lipopolysaccharide-stimulated iDCs. Anti-IL-10 antibodies increased the levels of IL-12p70 secretion in AgB- and SHF-matured DCs. AgB and SHF induced interleukin-1 receptor-associated kinase phosphorylation and activated nuclear factor-κB, suggesting that Toll-like receptors could participate in E. granulosus-stimulated DC maturation. These results suggest that E. granulosus escapes host immunosurveillance in two ways: by interfering with monocyte differentiation and by modulating DC maturation.


Immunology Letters | 2010

Estrogen receptor profiles in human peripheral blood lymphocytes

Marina Pierdominici; Angela Maselli; Tania Colasanti; Anna Maria Giammarioli; Federica Delunardo; Davide Vacirca; Massimo Sanchez; Antonello Giovannetti; Walter Malorni; Elena Ortona

Estrogens are well-known regulators of the immune responses. Most of their effects are mediated by two receptors: estrogen receptor (ER)alpha and ERbeta. Up to date the presence of intracellular ER in human immune cells represents a controversial issue, while their surface membrane expression has scarcely been explored. In this study we investigated the intracellular and cell surface expression of ERalpha and ERbeta in human peripheral blood lymphocytes (PBL) by flow and static cytometry as well as by Western Blot. To this aim we used five different commercial antibodies recognizing distinct ER epitopes. We observed that CD4(+) and CD8(+) T lymphocytes, B lymphocytes and NK cells contain intracellular ERalpha and ERbeta, being the ERalpha46 isoform the most represented ER. However, significant differences could be observed among the antibodies studied in terms of immunoreactivity and specificity. Importantly, we also found a cell surface expression of ERalpha46 isoform. We also observed that a membrane-impermeant form of E2 induced a rapid phosphorylation of extracellular signal-regulated kinase (ERK), a significant proliferation of T lymphocytes, and IFN-gamma production by NK cells, thus suggesting the expression of a functional mERalpha. In conclusion our data could provide new insights as concerns the estrogen-related mechanisms of immune system modulation. They also suggest the need for a reappraisal of the experimental conditions for the characterization of the ER expression.


The FASEB Journal | 2012

Role of autophagy in immunity and autoimmunity, with a special focus on systemic lupus erythematosus

Marina Pierdominici; M. Vomero; Cristiana Barbati; Tania Colasanti; Angela Maselli; Davide Vacirca; Antonello Giovannetti; Walter Malorni; Elena Ortona

Autophagy is a lysosome‐mediated catabolic process that allows cells to degrade unwanted cytoplasmic constituents and to recycle nutrients. Autophagy is also involved in innate and adaptive immune responses, playing a key role in interactions against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. Over recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmunity. Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by autoimmune responses against self‐antigens generated by dying cells. Genome‐wide association studies have linked several single‐nucleotide polymorphisms (SNPs) in the autophagy‐related gene Atg5 to SLE susceptibility. Loss of Atg5‐dependent effects, including clearance of dying cells and cell antigen presentation, might contribute to the autoimmunity and inflammation associated with SLE. Moreover, activation of the mammalian target of rapamycin (mTOR), a key player in the autophagy regulation, has recently been demonstrated in SLE, confirming an altered autophagy pathway in this disease. In the present review, we summarize the autophagy mechanisms, their molecular regulation, and their relevance in immunity and autoimmunity. The potential of targeting autophagy pathway in SLE, by developing innovative therapeutic approaches, has finally been discussed.—Pierdominici, M., Vomero, M., Barbati, C., Colasanti, T., Maselli, A., Vacirca, D., Giovannetti, A., Malorni, W., Ortona, E. Role of autophagy in immunity and autoimmunity, with a special focus on systemic lupus erythematosus. FASEB J. 26, 1400‐1412 (2012). www.fasebj.org


The FASEB Journal | 2012

T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy

Cristiano Alessandri; Cristiana Barbati; Davide Vacirca; Paola Piscopo; Annamaria Confaloni; Massimo Sanchez; Angela Maselli; Tania Colasanti; Fabrizio Conti; S. Truglia; Andras Perl; Guido Valesini; Walter Malorni; Elena Ortona; Marina Pierdominici

Autophagy, the cytoprotection mechanism that takes place under metabolic impairment, has been implicated in the pathogenesis of autoimmunity. Here, we investigated the spontaneous and induced autophagic behavior of T lymphocytes from patients with systemic lupus erythematosus (SLE) compared with that of T lymphocytes from healthy donors by measuring the autophagy marker microtubule‐associated protein 1 light chain 3 (LC3)‐II. No significant differences in spontaneous autophagy were found between T lymphocytes from patients with SLE and from healthy donors, apart from CD4+ naive T cells from patients with SLE in which constitutively higher levels of autophagy (P < 0.001) were detected. At variance, whereas treatment of T lymphocytes from healthy donors with serum IgG from patients with SLE resulted in a 2‐fold increase in LC3‐II levels (P<0.001), T lymphocytes from SLE patients were resistant to autophagic induction and also displayed an up‐regulation of genes negatively regulating autophagy, e.g., α‐synuclein. These findings could open new perspectives in the search for pathogenetic determinants of SLE progression and in the development of therapeutic strategies aimed to recover T‐cell compartment homeostasis by restoring autophagic susceptibility.—Alessandri, C., Barbati, C., Vacirca, D., Piscopo, P., Confaloni, A., Sanchez, M., Maselli, A., Colasanti, T., Conti, F., Truglia, S., Perl, A., Valesini, G., Malorni, W., Ortona, E., Pierdominici, M. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J. 26, 4722–4732 (2012). www.fasebj.org


Clinical and Experimental Immunology | 2008

Immunological markers indicating the effectiveness of pharmacological treatment in human hydatid disease

Rachele Riganò; Elisabetta Profumo; S. Ioppolo; S. Notargiacomo; Elena Ortona; Antonella Teggi; Alessandra Siracusano

The relation of interferon‐gamma (IFN‐γ), IL‐4, IL‐10 production and specific IgE, total IgG, IgG subclass expression to the effectiveness of pharmacological treatment in human hydatid disease (Echinococcus granulosus infection) was evaluated in 27 hydatid patients divided into four clinical groups according to their response to albendazole/mebendazole therapy (full, partial, low and non‐responders). After parasite antigen stimulation, peripheral blood mononuclear cells (PBMC) from full responders produced significantly more IFN‐γ (P= 0·038), significantly less IL‐4 (P= 0·001) and less IL‐10 than PBMC from non‐responders. PBMC from partial and low responders produced intermediate cytokine concentrations. ELISA determining immunoglobulin production showed that sera from all non‐responders had IgE and IgG4 antibodies, both regulated by IL‐4. In contrast to IgG4, IgE decreased rapidly in full responders. Full responders also showed the highest percentage of IgG3 reactions. Qualitative analysis of total IgG responses in hydatid patients’ sera determined by immunoblotting showed that binding profiles to hydatid cyst fluid antigen differed in the four groups of treated patients. Non‐responders had the highest percentage of reactions to all subunits of antigens 5 and B, and full responders had the highest percentage of reactions to antigen 5 alone. The high IFN‐γ production associated with a lack of IL‐4 and low IL‐10 production in the full responders, and vice versa the high IL‐4 and IL‐10 production associated with lack of or low IFN‐γ production in the non‐responders implies Th1 cell activation in protective immunity and Th2 cell activation in susceptibility to hydatid disease. IgE may be a useful marker of therapeutic success in hydatid patients with pretreatment specific IgE antibodies. IgG subclass responses and differential immunoglobulin subclass binding pattern to hydatid antigens may also be useful in the immunosurveillance of hydatid disease.


Autoimmunity Reviews | 2008

Redox state, cell death and autoimmune diseases: a gender perspective.

Elena Ortona; Paola Margutti; Paola Matarrese; Flavia Franconi; Walter Malorni

Autoimmune disorders, redox balance and gender differences are closely connected. In fact, activation, proliferation and death of cells of different histotype, including blood and vascular cells, are under control of oxidative balance and are key players in autoimmune disease pathogenesis and progression. However, cells from male and female appear characterized by a huge series of differences in terms of reactive oxygen species production and oxidative stress susceptibility. In this review, we briefly summarize the possible implications of the redox state in the onset and progression of autoimmune diseases in a gender perspective.


Acta Tropica | 2003

An update on immunodiagnosis of cystic echinococcosis.

Elena Ortona; Rachele Riganò; Brigitta Buttari; Federica Delunardo; Salvatore Ioppolo; Paola Margutti; Elisabetta Profumo; Antonella Teggi; Sergio Vaccari; Alessandra Siracusano

Immunological parameters are increasingly investigated as possible markers for the development of cystic echinococcosis. Among the newer immunologic tests for assessing the host-parasite relationship, assay of immunoglobulin isotypes with the use of distinct parasite antigens and detection of Th1/Th2 cytokine expression are an interesting new approach. The findings upon which we have constructed our immunological hypothesis of the host-parasite relationship are: (1) immunoglobulin isotype profiles differ in patients with distinct clinical outcomes of the disease; in particular, antigen B is the antigen of choice to detect specific IgG4, which is the immunoglobulin isotype most clearly associated with the progression of the disease; (2) the isolation and characterisation of recombinant parasite proteins that behave as molecular markers of allergic reactions associated with cystic echinococcosis; (3) Th1/Th2 cell activation is involved in the clinical outcome of Echinococcus granulosus infection and, in particular Th2 response, is associated with susceptibility to the disease, whereas a Th1 response is associated with protective immunity.


Parasite Immunology | 2004

Echinococcus granulosus‐specific T‐cell lines derived from patients at various clinical stages of cystic echinococcosis

Rachele Riganò; Brigitta Buttari; E. De Falco; Elisabetta Profumo; Elena Ortona; Paola Margutti; C. Scottà; Antonella Teggi; Alessandra Siracusano

To investigate the role of T lymphocytes in the immune response to Echinococcus granulosus, using sheep hydatid fluid (SHF) and antigen B (AgB), we generated T‐cell lines from patients with active, transitional and inactive hydatid cysts. We established 16 T‐cell lines, eight specific to SHF and eight specific to AgB. At surface phenotyping 88–98% of cells displayed the helper/inducer CD4 antigen. In all patients, at all clinical stages of hydatid cyst disease, T‐cell stimulation with SHF and AgB invariably amplified a large number of almost identical Vβ subfamily fragments. Irrespective of antigen‐specificity, the two cell lines from the patient with an inactive cyst had a Th1 profile, because they exclusively expressed and produced IFN‐γ. Conversely, the T‐cell lines derived from the seven patients with active and transitional hydatid cysts had mixed Th1/Th2 and Th0 clones. The functional characteristics of the 16 T‐cell lines differed markedly in the various clinical stages of cystic echinococcosis, thus providing new in vitro evidence that Th1 lymphocytes contribute decisively to the inactive stage of hydatid disease, Th2 lymphocytes in the active and transitional stages. The parasite‐specific T‐cell lines, especially the two Th1 lines from the patient with an inactive cyst, may help identify Th1 protective epitopes on SHF and AgB.


Parasite Immunology | 1996

Immunological responses to antigen B from Echinococcus granulosus cyst fluid in hydatid patients

Salvatore Ioppolo; S. Notargiacomo; Elisabetta Profumo; C. Franchi; Elena Ortona; Rachele Riganò; Alessandra Siracusano

The immunological reactivity of Echinococcus granulosus antigen B was evaluated in 30 hydatid patients. Antigen B was purified from sheep hydatid cyst fluid by electroelution from a non‐reducing SDS‐PAGE gel (AgB). In ELISA and immunoblotting (IB), determining antibody production in sera from patients with hydatid disease and with other parasitic infections, purified AgB showed higher specificity than a partially purified antigen named pH5PPT (100% vs 83% in pH5PPT‐ELISA and 58% in pH5PPT‐IB). AgB‐IB achieved higher sensitivity than AgB‐ELISA (80% vs 63%). All AgB‐IB positive sera recognized the 12 kDa subunit. Qualitative AgB‐IB assessment of IgG isotype responses identified IgG4 as the predominant isotype (87%). The other isotypes showed a lower percentage of positive reactions: IgG1, 33%; IgG2, 21%; and IgG3, 17%. PBMC proliferative assay revealed a cellular response to AgB in 100% of patients’ PBMC. These findings confirm antigen B, especially its smallest subunit, as a good diagnostic molecule.


Clinical and Experimental Immunology | 2008

In vitro production of cytokines by peripheral blood mononuclear cells from hydatid patients

Rachele Riganò; Elisabetta Profumo; G. Di Felice; Elena Ortona; A Teggi; Alessandra Siracusano

The role of cytokines in human hydatidosJs (Echinococcus granulosus infection) was evaluated in immunoassays determining production of IL‐4, IL‐10 and interferon‐gamma (IFN‐γ) in peripheral blood mononuclear cell (PBMC) cultures from 30 hydatid patients and 14 uninfected controls. In ceil cultures from hydatid patients parasite and non‐parasite antigen stimulation significantly increased IL‐4 production (P·0·005). Spontaneous and milogen‐driven IL‐4 production was similar in patients and controls. IL‐10 and IFN‐γ production did not differ statistically in the two groups, even though some hydatid patients produced these cytokines in large amounts. Notably, antigen‐driven IFN‐γ concentrations were invariably higher in patients than in uninfected controls. Data analysis showed a relationship between IgE and IgG4 responses and parasite‐driven cytokine production. High IgE and IgG4 responders produced high IL‐4 and IL‐10 concentrations. High IgE responders showed decreased IFN‐γ production, but high IgG4 responders had IFN‐γ levels slightly higher than those of low responders. Cytokine response patterns did not relate to the clinical stage of disease. The significantly increased IL‐4 and the high IL‐10 concentrations found in PBMC from many hydatid patients in this study are consistent with Th2 cell activation in human hydatidosis. The presence of antigen‐driven IFN‐γ production in patients with E. granulosus infection implies concurrent intervention of the Th1 or Th0 cell subset.

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Alessandra Siracusano

Istituto Superiore di Sanità

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Paola Margutti

Istituto Superiore di Sanità

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Federica Delunardo

Istituto Superiore di Sanità

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Rachele Riganò

Istituto Superiore di Sanità

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Elisabetta Profumo

Istituto Superiore di Sanità

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Marina Pierdominici

Istituto Superiore di Sanità

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Walter Malorni

Istituto Superiore di Sanità

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Brigitta Buttari

Istituto Superiore di Sanità

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