DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells

BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs). RESULTS: Pathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules. CONCLUSIONS: The initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies

Modulation of the immune and inflammatory responses by Plasmodium falciparum schizont extracts: role of myeloid dendritic cells in effector and regulatory functions of CD4+ lymphocytes.

The optimal immune response to malaria infection comprises rapid induction of inflammatory responses promptly counteracted by regulatory mechanisms to prevent immunopathology. To evaluate the role of dendritic cells (DC) in the balance of parasite-induced inflammatory/anti-inflammatory mechanisms, we studied the activity of monocyte-derived dendritic cells (MDDC), previously exposed to soluble extracts of Plasmodium falciparum-infected red blood cells (PfSE), in the differentiation of CD4 cells isolated from donors never exposed to malaria infection. We show that MDDC exposed to PfSE are extremely efficient to induce a contemporary differentiation of TH1 effector cells and T regulatory (Treg) cells in CD4 T cells even when exposed to low concentrations of parasitic extracts. Treg cells induced by MDDC infected with PfSE (MDDC-PfSE) produce transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) and are endowed with strong suppressive properties. They also show phenotypical and functional peculiarities, such as the contemporary expression of markers of Treg and TH1 differentiation and higher sensitivity to TLR4 ligands both inducing an increasing production of suppressive cytokines. On the whole, our data indicate that MDDC exposed to PfSE orchestrate a well-balanced immune response with timely differentiation of TH1 and Treg cells in CD4 cells from nonimmune donors and suggest that, during the infection, the role of MDCC could be particularly relevant in low-parasitemia conditions

Nostra esperienza nel trattamento del varicocele in regime di day-surgery

Negli ultimi anni l’interesse crescente per le metodiche mininva - sive ha spinto a rivalutare la tecnica chirurgica di varicocelectomia sottoinguinale nel trattamento del varicocele idiopatico. Gli Autori, tra il 1998 ed il 2001, hanno sottoposto a varicocelec - tomia sottoinguinale 29 pazienti di cui 14 affetti da varicocele idiopa - tico di III grado, 11 di II grado, 3 di I grado ed 1 subclinico. Dei 29 pazienti solo 10 presentavano anamnesi sfavorevole per paternità. Tutti gli interventi sono stati eseguiti in anestesia locale e in regime di day-surgery. Gli Autori discutono i risultati e concludono che la varicocelecto - mia sottoinguinale con dispositivi ottici di ingrandimento rappresen - ta il “gold standard” nel trattamento del varicocele idiopatico, in quanto consente di ridurre al minimo il tasso di recidive, di limitare l’incidenza delle complicanze post-operatorie, di migliorare qualiquantitativamente le capacità riproduttive del liquido seminale, di abbassare significativamente i costi di gestione dell’ammalato, di mantenere in limiti accettabili la durata dell’intervento e di essere di facile apprendimento ed esecuzione