Understanding the Functional Properties of Neonatal Dendritic Cells: A Doorway to Enhance Vaccine Effectiveness?

Increased susceptibility to infectious diseases is a hallmark of the neonatal period of life that is generally attributed to a relative immaturity of the immune system. Dendritic cells (DCs) are innate immune sentinels with vital roles in the initiation and orchestration of immune responses, thus, constituting a promising target for promoting neonatal immunity. However, as is the case for other immune cells, neonatal DCs have been suggested to be functionally immature compared to their adult counterparts. Here we review some of the unique aspects of neonatal DCs that shape immune responses in early life and speculate whether the functional properties of neonatal DCs could be exploited or manipulated to promote more effective vaccination in early life

Understanding the Functional Properties of Neonatal Dendritic Cells: A Doorway to Enhance Vaccine Effectiveness?

Increased susceptibility to infectious diseases is a hallmark of the neonatal period of life that is generally attributed to a relative immaturity of the immune system. Dendritic cells (DCs) are innate immune sentinels with vital roles in the initiation and orchestration of immune responses, thus, constituting a promising target for promoting neonatal immunity. However, as is the case for other immune cells, neonatal DCs have been suggested to be functionally immature compared to their adult counterparts. Here we review some of the unique aspects of neonatal DCs that shape immune responses in early life and speculate whether the functional properties of neonatal DCs could be exploited or manipulated to promote more effective vaccination in early life

Clec9a-mediated ablation of conventional dendritic cells suggests a lymphoid path to generating dendritic cells In Vivo

Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired

The host galaxies of three radio-loud quasars: 3C 48, 3C 345, and B2 1425+267

Observations with the Wide-Field/Planetary Camera-2 of the Hubble Space Telescope (HST) are presented for three radio-loud quasars: 3C 48 (z=0.367), B2 1425+267 (z=0.366), and 3C 345 (z=0.594). All three quasars have luminous (~4 L^*) galaxies as hosts, which are either elliptical (B2 1425+267 and 3C 345) or interacting (3C 48), and all hosts are 0.5 - 1.0 mag bluer in (V-I) than other galaxies with the same overall morphology at similar redshifts to the quasars. The host of 3C 48 has many H II regions and a very extended tidal tail. All nine of the radio-loud quasars studied here and in Bahcall et al. (1997) either have bright elliptical hosts or occur in interacting systems. There is a robust correlation between the radio emission of the quasar and the luminosity of host galaxy; the radio-loud quasars reside in galaxies that are on average about 1 mag brighter than hosts of the radio-quiet quasars.Comment: Accepted for publication in ApJ. 3 postscript and 3 jpeg figures. Original figures may be found in ftp://eku.sns.ias.edu/pub/sofia/RadioLoud

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).

An open-source solution for advanced imaging flow cytometry data analysis using machine learning

Imaging flow cytometry (IFC) enables the high throughput collection of morphological and spatial information from hundreds of thousands of single cells. This high content, information rich image data can in theory resolve important biological differences among complex, often heterogeneous biological samples. However, data analysis is often performed in a highly manual and subjective manner using very limited image analysis techniques in combination with conventional flow cytometry gating strategies. This approach is not scalable to the hundreds of available image-based features per cell and thus makes use of only a fraction of the spatial and morphometric information. As a result, the quality, reproducibility and rigour of results are limited by the skill, experience and ingenuity of the data analyst. Here, we describe a pipeline using open-source software that leverages the rich information in digital imagery using machine learning algorithms. Compensated and corrected raw image files (.rif) data files from an imaging flow cytometer (the proprietary .cif file format) are imported into the open-source software CellProfiler, where an image processing pipeline identifies cells and subcellular compartments allowing hundreds of morphological features to be measured. This high-dimensional data can then be analysed using cutting-edge machine learning and clustering approaches using “user-friendly” platforms such as CellProfiler Analyst. Researchers can train an automated cell classifier to recognize different cell types, cell cycle phases, drug treatment/control conditions, etc., using supervised machine learning. This workflow should enable the scientific community to leverage the full analytical power of IFC-derived data set. It will help to reveal otherwise unappreciated populations of cells based on features that may be hidden to the human eye that include subtle measured differences in label free detection channels such as bright-field and dark-field imagery

Semi-Dense 3D Reconstruction with a Stereo Event Camera

Event cameras are bio-inspired sensors that offer several advantages, such as low latency, high-speed and high dynamic range, to tackle challenging scenarios in computer vision. This paper presents a solution to the problem of 3D reconstruction from data captured by a stereo event-camera rig moving in a static scene, such as in the context of stereo Simultaneous Localization and Mapping. The proposed method consists of the optimization of an energy function designed to exploit small-baseline spatio-temporal consistency of events triggered across both stereo image planes. To improve the density of the reconstruction and to reduce the uncertainty of the estimation, a probabilistic depth-fusion strategy is also developed. The resulting method has no special requirements on either the motion of the stereo event-camera rig or on prior knowledge about the scene. Experiments demonstrate our method can deal with both texture-rich scenes as well as sparse scenes, outperforming state-of-the-art stereo methods based on event data image representations.Comment: 19 pages, 8 figures, Video: https://youtu.be/Qrnpj2FD1e

The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment, favoring cross-presentation to CD8 + T cells. DNGR-1 regulated crosspriming in non-infectious settings such as immunization with antigen-bearing dead cells, as well as in highly immunogenic situations such as infection with herpes simplex virus type 1. Together, these results suggest that DNGR-1 is a dedicated receptor for cross-presentation of cell-associated antigens. Our work thus underscores the importance of cross-priming in immunity and indicates that antigenicity and adjuvanticity can be decoded by distinct innate immune receptors. The identification of specialized receptors that regulate antigenicity of virus-infected cells reveals determinants of antiviral immunity that might underlie the human response to infection and vaccination

Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired