Pulmonary dendritic cells: thinking globally, acting locally

The phrase “think globally, act locally” was coined in the early 1970s and directed individuals to clean up their local environment with the ultimate goal of improving the health of the entire planet. Several recent studies indicate that similar considerations apply to the immune system, in which small numbers of leukocytes, such as pulmonary dendritic cells, can modify the local immune environment in the lung and promote a positive outcome for the organism

A Prominent Role for DC-SIGN+ Dendritic Cells in Initiation and Dissemination of Measles Virus Infection in Non-Human Primates

Measles virus (MV) is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150+T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC) C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGNhiDCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGNhicells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values &gt;0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.</p

Visualisation and characterisation of mononuclear phagocytes in the chicken respiratory tract using CSF1R-transgenic chickens

Additional file 2. Location of B cells, T cells and follicular dendritic cells (FDC) in the lung of MacReporter chickens. The BALT region of 5 to 7 week old non-vaccination animals were analysed for B, T and FCD cells. Isotype controls were used to standardise the microscope and examine aspecific binding before acquiring images (A-B). The GC of MacReporter animals are tightly packed with Bu1-CSF1R-eGFP+ FDC cells and Bu1+CSF1R-eGFP- B cells (C) with few Bu1+ B cells found in the parabronchi (F). CD3+ T cells are disperse within and outside the GC (D) and parabronchi (G). CSF1R-eGFP+ FDC cells express Fc receptors and trap immunoglobulin by expressing IgY (E) and CSF1R-eGFP+ IgY+ FDC are rarely detected out with the GC, BALT region of the lung. GC are indicated by white dashed lines

Understanding immune cells in tertiary lymphoid organ development:it is all starting to come together

Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organisation, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum and high endothelial venules. In this respect, they mimic the activities of germinal centres and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to either beneficial or deleterious outcomes. While the development and architectural organisation of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid and inflammatory cytokines and adhesion molecules, our understanding of the cells responsible for triggering these events is still evolving. Over the past 10-15 years novel immune cell subsets have been discovered that have more recently been implicated in the control of TLO development and function. In this review we will discuss the contribution of these cell types and consider the potential to develop new therapeutic strategies that target TLOs

Visual Alterity Abroad: Hegel through Birgit Hein's Baby I will Make You Sweat and La Moderna Poesia

Foucault's discussion of the panopticon is the best-known engagement with visual epistemology, the relationship of sight and knowledge. Yet the panopticon is only one form of visual epistemology and all technologies of perspective position and situate their subjects.&nbsp; As a colloquial statement of visual epistemology we might say: you are how you see. This essay focuses on the cinematic episteme or how the technology of cinema configures a way of seeing and way of knowing. Specifically this essay takes up a narrower question of visual alterity.&nbsp; Beginning from Hegel's discussion of consciousness, it asks how within and through film we recognise our self and how can we see the other? To carry out the analysis, the essay attends in particular to two films Baby I will Make You Sweat (1994) and La Moderna Poesia (2000) by experimental and underground artist Birgit Hein. These films combine incongruous and even conflicting representational strategies that particularly enable an exploration of visual alterity. Both films on the one hand narrate a highly subjective experience of self/other relations within the context of a travel narrative: a woman seeking to recapture some sense of life, travels to an unfamiliar destination, enters into new environments and takes up relationships, sometimes intimate, with strangers.&nbsp; On the other hand they both rely on a form of aesthetic abstraction that leaves the film without renaissance perspective, panoptic organizing, shot-reverse shot, continuity editing, i.e. an of the typical representational strategies of alterity found in narrative films

Creating Europe through Creative Europe

In this final session in our Spring series on “Creating Europe through…” our panel of experts will focus on European-level cultural policy and and its impact on local and global cultural sectors. Taking the European Commission’s Creative Europe program as a starting point, including initiatives such as the ECoC, the conversation will explore intersections of policy-making, cultural diplomacy, cultural trade, tourism, and implications for European identity and solidarity. Audience participation is encouraged