Cutting edge: differential chemokine production by myeloid and plasmacytoid dendritic cells.

Abstract To examine the different roles of myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) in the induction and regulation of immune response, we have studied chemokine secretion by freshly isolated DC subsets in response to bacterial, viral, and T cell-derived stimuli. M-DCs selectively produced very high levels of the homeostatic chemokines CC chemokine ligand (CCL)17 and CCL22, while P-DCs produced very little if any. In contrast, the proinflammatory chemokine CCL3 was secreted mostly by P-DCs, whereas CCL4 and CXC chemokine ligand 8 were produced by both subsets. The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections. The high production of CCR4 ligands by M-DCs suggests their capacity to selectively recruit at sites of inflammation T cells with regulatory properties or with a Th2 phenotype, whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells

Fulminant septic shock caused by Capnocytophaga canimorsus in Italy: Case report

Capnocytophaga canimorsus infection was recently recognized as a zoonosis. We report the first case of fulminant septic shock in Italy caused by this pathogen. The patient, with a history of splenectomy, died at the main hospital in Brescia with a presumptive diagnosis of sepsis. PCR and sequencing on post mortem samples confirmed C. canimorsus as a causative organism. Our purpose is to alert medical professionals to the virulence of C. canimorsus in asplenic and immunocompromised patients. Keywords: Capnocytophaga canimorsus, septic shock, PCR, sequencin

E-cadherin expression and blunted interferon response in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm derived from plasmacytoid dendritic cells (pDCs). In this study, we investigated by immunohistochemical analysis the expression of E-cadherin (EC) on pDCs in reactive lymph nodes and tonsils, bone marrow, and in BPDCN. We compared the expression of EC in BPDCN to that in leukemia cutis (LC) and cutaneous lupus erythematosus (CLE), the latter typically featuring pDC activation. In BPDCN, we also assessed the immunomodulatory activity of malignant pDCs through the expression of several type I interferon (IFN-I) signaling effectors and downstream targets, PD-L1/CD274, and determined the extent of tumor infiltration by CD8-expressing T cells. In reactive lymph nodes and tonsils, pDCs expressed EC, whereas no reactivity was observed in bone marrow pDCs. BPDCN showed EC expression in the malignant pDCs in the vast majority of cutaneous (31/33 cases, 94%), nodal, and spleen localizations (3/3 cases, 100%), whereas it was more variable in the bone marrow (5/13, 38,5%), where tumor cells expressed EC similarly to the skin counterpart in 4 cases and differently in other 4. Notably, EC was undetectable in LC (n=30) and in juxta-epidermal pDCs in CLE (n=31). Contrary to CLE showing robust expression of IFN-I-induced proteins MX1 and ISG5 in 20/23 cases (87%), and STAT1 phosphorylation, BPDCN biopsies showed inconsistent levels of these proteins in most cases (85%). Expression of IFN-I-induced genes, IFI27, IFIT1, ISG15, RSAD2, and SIGLEC1, was also significantly (P\u3c0.05) lower in BPDCN as compared with CLE. In BPDCN, a significantly blunted IFN-I response correlated with a poor CD8+T-cell infiltration and the lack of PD-L1/CD274 expression by the tumor cells. This study identifies EC as a novel pDC marker of diagnostic relevance in BPDCN. The results propose a scenario whereby malignant pDCs through EC-driven signaling promote the blunting of IFN-I signaling and, thereby, the establishment of a poorly immunogenic tumor microenvironment

GPR56 as a novel marker identifying the CD56dull CD16+ NK cell subset both in blood stream and in inflamed peripheral tissues

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Degree correlations in signed social networks

We investigate degree correlations in two online social networks where users are connected through different types of links. We find that, while subnetworks in which links have a positive connotation, such as endorsement and trust, are characterized by assortative mixing by degree, networks in which links have a negative connotation, such as disapproval and distrust, are characterized by disassortative patterns. We introduce a class of simple theoretical models to analyze the interplay between network topology and the superimposed structure based on the sign of links. Results uncover the conditions that underpin the emergence of the patterns observed in the data, namely the assortativity of positive subnetworks and the disassortativity of negative ones. We discuss the implications of our study for the analysis of signed complex networks

Mnemonic Wars, Ephemeral Narratives and Contested Terrains. Collective Memory as a Conflictual Space of Confrontation

As noted by Mouffe (2005) and Ranciére (2004), the new millennium inaugurated a post-political phase where the idea of consensus replaced that of conflict: the political, understood in its agonistic dimension, is reduced to a series of administrative procedures, in which moments of tension and conflict lose their critical potential and are resolved through a technical and rational calculation. One of the most common expressions with which the post-political phase of consensus has manifested itself, especially in the European context, is the idea of shared memory. In the last twenty years, the development of digital media has radically affected the way collective memory can be constructed, represented, narrated, and disseminated (Blom, 2016). While the intrinsic risks of the digital revolution have been widely discussed (in terms of fake news, historical revisionism, and in general post-truth), the possibility to understand and to approach historical documents and materials as living matter opens up new research trajectories and design approaches able to question the idea of shared memory, and to move closer to the image of entangled memory and mnemography (Feindt et al., 2014). This paper analyses and discusses some projects and practices in the field of infographic design and counter-forensic that could lead to a conflictual or adversarial understanding of collective memory as a contested terrain

Cutting Edge: Differential Chemokine Production by Myeloid and Plasmacytoid Dendritic Cells

Abstract To examine the different roles of myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) in the induction and regulation of immune response, we have studied chemokine secretion by freshly isolated DC subsets in response to bacterial, viral, and T cell-derived stimuli. M-DCs selectively produced very high levels of the homeostatic chemokines CC chemokine ligand (CCL)17 and CCL22, while P-DCs produced very little if any. In contrast, the proinflammatory chemokine CCL3 was secreted mostly by P-DCs, whereas CCL4 and CXC chemokine ligand 8 were produced by both subsets. The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections. The high production of CCR4 ligands by M-DCs suggests their capacity to selectively recruit at sites of inflammation T cells with regulatory properties or with a Th2 phenotype, whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells

IL-21 promotes Granzyme B-dependent NK/plasmacytoid dendritic cell functional interaction in cutaneous lupus erythematosus

Autoimmune skin lesions are characterized by a complex cytokine milieu and by the accumulation of plasmacytoid dendritic cells (pDCs). Granzyme B (GrB) transcript is abundant in activated pDCs, though its mechanisms of regulation and biological role are largely unknown. Here we report that IL-21 was the only Th1/Th17 cytokine able to induce the expression and secretion of GrB by pDCs and that this action was counteracted by the autocrine production of type I interferons (IFNs). In lupus erythematosus (LE) skin lesions, the percentage of GrB(+) pDCs directly correlated with the IL-21/MxA ratio, indicating that the interplay between these two cytokines finely tune the levels of pDC-dependent GrB also in vivo. In LE, pDCs colocalized with professional cytotoxic cells at sites of epithelial damage, suggesting a role in keratinocyte killing. In accordance, we demonstrate that supernatants of IL-21-activated pDCs promoted autologous keratinocyte killing by NK cells and this action was dependent on GrB. These results propose a GrB-dependent functional interaction between pDCs and NK cells and highlight a negative feedback regulation by type I IFNs in vitro and in vivo that may function to limit excessive tissue damage