Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions

International audienceDendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks, and com-plementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization, and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation, and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes, and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types, organs, and species

Effect of the Chemical Composition of Building Materials on Algal Biofouling

International audienceThe main cause of aesthetical deterioration of outdoor exposed building materials is the colonization by microorganisms. This phenomenon depends on factors such as geographical situation, environmental conditions and surface state of the substrate. Several researches have been devoted to the study of the effect of porosity, roughness and surface treatment on the biofouling of building materials. However, none of them has addressed the influence of cement composition. The main objective of this study is thus to highlight the influence of the composition of the material on its biocolonization by algae. The green alga Klebsormidium flaccidum was chosen because of its representativeness in France. It is indeed the species the most frequently identified and isolated from samples taken on sites. In order to characterize the influence of the composition of building materials on their biofouling, the behavior of mortars prepared with two types of Portland cement and two types of calcium aluminates cement is studied. The biofouling is followed by measuring the covering rate thanks to image analysis. This work is realized both on samples exposed outdoor and on samples tested in a laboratory bench. Obtained results prove that the composition of cementitious materials is a determining factor

Interactivity in Digital Storytelling:An Influencing Factor of Qualityof Experience

Storytelling has always existed in human culture, and it has applications in many areas, including tourism and education. In recent years, thanks to the rapid development of technologies, digital tools have become part of the storytelling process, and digital storytelling is thus made possible. Interactive narratives are commonly found in digital storytelling, in which participants can become part of the story, play an active role, alter the path of the story, or generate their own contents and leave an impact on the story. Tourism is one of the areas that could benefit from location based digital storytelling. It enriches tourist destinations, and provides an experience that is tightly connected to the specific locations. An augmented reality (AR) application on a mobile device, was developed in Unity. It is built based on the previous prototype that tells a simple troll story in Trollheimen. In this prototype, only GPS data is used, to collect the location information of the mobile device. The application displays different media content based on the location information. The story of this prototype is improved, with more contents, and new ways of interaction and implementation. Some of the story contents were provided by iTrollheimen, and Nord Universitet. This prototype was used to conduct experiments for proving the hypothesis: richer interactivity leads to a better Quality of Experience (QoE) in digital storytelling. 18 participants were recruited to take part in the experiments. Two variations of the prototype were made, one with richer interactivity while the other with reduced options of interaction. The participants were split up into 2 groups, and each group did the experiments with one version of the prototype. The results indicate that the richer interactivity prototype offered better Quality of Experience to the users

Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections

Type-I interferons (IFN-I) are cytokines essential for vertebrate antiviral defense, including against herpesviruses. IFN-I have potent direct antiviral activities and also mediate a multiplicity of immunoregulatory functions, which can either promote or dampen antiviral adaptive immune responses. Plasmacytoid dendritic cells (pDCs) are the professional producers of IFN-I in response to many viruses, including all of the herpesviruses tested. There is strong evidence that pDCs could play a major role in the initial orchestration of both innate and adaptive antiviral immune responses. Depending on their activation pattern, pDC responses may be either protective or detrimental to the host. Here, we summarize and discuss current knowledge regarding pDC implication in the physiopathology of mouse and human herpesvirus infections, and we discuss how pDC functions could be manipulated in immunotherapeutic settings to promote health over disease

Influence de la composition chimique de mortiers sur leur biodétérioration par les algues

The fouling of building-facade is caused by a main aesthetic phenomenon of biological weathering. The natural weathering favors the micro-organisms development. The biofouling kinetics depends on several parameters such as geographical situation, environmental conditions and physicochemical parameters of substrates. The main objective of this study is to highlight the influence of the mortar chemistry in relationship with its physical properties on the algal growth. The biofouling kinetics was followed on samples exposed outdoor and on samples tested in a laboratory bench which consists in spraying an algal culture on mortar specimens. In order to characterize the influence of the mortar chemistry on biofouling, two Portland cements (OPC) and two calcium aluminate cements (CAC) were tested. The influence of roughness, porosity and carbonation was also studied. The green algae Klebsormidium flaccidum were chosen for the accelerated laboratory tests because of its representativeness. The results obtain in laboratory and in situ show that CAC based mortars slow down the colonization kinetics compared to OPC based mortars. When porosity increases the biofouling kinetics increases and the effect of the mortars chemical composition is largely hidden. The carbonated mortars biofouling is achieved more quickly than uncarbonated ones especially for OPC based mortars. Finally, the rough surfaces are colonized faster whatever formulation tested. This parameter is mostly highlighted for in situ tests.L’encrassement des façades d’immeuble est causé par un phénomène d’altération biologique essentiellement esthétique. Leur vieillissement naturel favorise la colonisation de micro-organismes. La cinétique de biodétérioration dépend de plusieurs paramètres, tels que la situation géographique, les conditions environnementales et les caractéristiques physico-chimiques du matériau. L’objectif de la présente étude est d’établir un lien entre la composition chimique de mortiers à base de ciments et leur cinétique de colonisation par des microorganismes. Deux bancs d’essais sont utilisés : un banc d’essai in situ et un banc d’essai de biodétérioration accélérée de laboratoire. Deux ciments Portland (OPC) et deux ciments alumineux (CAC) de minéralogies différentes ont été sélectionnés. L’effet de la porosité, de la rugosité et de la carbonatation a également été étudié. Le microorganisme sélectionné pour les essais de laboratoire est l’algue Klebsormidium flaccidum qui se développe de manière prépondérante sur les façades en France. Les résultats obtenus en laboratoire et in situ montrent que la biocolonisation des mortiers à base de CAC est plus lente que celle des mortiers à base d’OPC. Lorsque la porosité augmente, la vitesse de biocolonisation augmente et l’effet de la composition chimique est en grande partie masqué. La biocolonisation des mortiers carbonatés se réalise plus rapidement que celle des mortiers non carbonatés surtout dans le cas des mortiers à base d’OPC. Enfin, les mortiers de surface rugueuse sont colonisés plus rapidement quelle que soit la formulation testée. Cet effet est plus marqué pour les mortiers exposés in situ que pour ceux testés en laboratoire

Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12

CD8alpha(+) and CD103(+) dendritic cells (DCs) play a central role in the development of type 1 immune responses. However, their role in type 2 immunity remains unclear. We examined this issue using Batf3(-/-) mice, in which both of these DC subsets are missing. We found that Th2 cell responses, and related events such as eosinophilia, alternative macrophage activation, and immunoglobulin class switching to IgG1, were enhanced in Batf3(-/-) mice responding to helminth parasites. This had beneficial or detrimental consequences depending on the context. For example, Batf3 deficiency converted a normally chronic intestinal infection with Heligmosomoides polygyrus into an infection that was rapidly controlled. However, liver fibrosis, an IL-13-mediated pathological consequence of wound healing in chronic schistosomiasis, was exacerbated in Batf3(-/-) mice infected with Schistosoma mansoni. Mechanistically, steady-state production of IL-12 by migratory CD103(+) DCs, independent of signals from commensals or TLR-initiated events, was necessary and sufficient to exert the suppressive effects on Th2 response development. These findings identify a previously unrecognized role for migratory CD103(+) DCs in antagonizing type 2 immune responses

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

textabstractThe classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research

Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming

Dendritic cells (DC) are key regulators of both protective immune responses and tolerance to self‐antigens. Soon after their discovery in lymphoid tissues by Steinman and Cohn, as cells with the unique ability to prime naïve antigen‐specific T cells, it was realized that DC can exist in at least two distinctive states characterized by morphological, phenotypic and functional changes—this led to the description of DC maturation. It is now well appreciated that there are several subsets of DC in both lymphoid and non‐lymphoid tissues of mammals, and these cells show remarkable functional specialization and specificity in their roles in tolerance and immunity. This review will focus on the specific characteristics of DC subsets and how their functional specialization may be regulated by distinctive gene expression programs and signaling responses in both steady‐state and in the context of inflammation. In particular, we will highlight the common and distinctive genes and signaling pathways that are associated with the functional maturation of DC subsets

Interferon α/β and Interleukin 12 Responses to Viral Infections: Pathways Regulating Dendritic Cell Cytokine Expression In Vivo

Interferon (IFN)-α/β and interleukin (IL)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. The studies presented here identified a novel subset of dendritic cells (DCs) as major producers of the cytokines during murine cytomegalovirus (MCMV) but not lymphocytic choriomeningitis virus (LCMV) infections. These DCs differed from those activated by Toxoplasma antigen but were related to plasmacytoid cells, as assessed by their CD8α+Ly6G/C+CD11b− phenotype. Another DC subset (CD8α2Ly6G/C−CD11b+) also contributed to IL-12 production in MCMV-infected immunocompetent mice, modestly. However, it dramatically increased IL-12 expression in the absence of IFN-α/β functions. Conversely, IFN-α/β production was greatly reduced under these conditions. Thus, a cross-regulation of DC subset cytokine responses was defined, whereby secretion of type I IFNs by CD8α+ DCs resulted in responses limiting IL-12 expression by CD11b+ DCs but enhancing overall IFN-α/β production. Taken together, these data indicate that CD8α+Ly6G/C+CD11b− DCs play important roles in limiting viral replication and regulating immune responses, through cytokine production, in some but not all viral infections. They also illustrate the plasticity of cellular sources for innate cytokines in vivo and provide new insights into the roles of IFNs in shaping immune responses to viruses