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International audience; The development of protein and microorganism engineering have led to rising expectations of biotechnology in the design of emerging biomaterials, putatively of high interest to reduce our dependence on fossil carbon resources. In this way, cellulose, a renewable carbon based polysaccharide and derived products, displays unique properties used in many industrial applications. Although the functionalization of cellulose is common, it is however limited in terms of number and type of functions. In this work, a Carbohydrate-Binding Module (CBM) was used as a central core to provide a versatile strategy to bring a large diversity of functions to cellulose surfaces. CBM3a from Clostridium thermocellum, which has a high affinity for crystalline cellulose, was flanked through linkers with a streptavidin domain and an azide group introduced through a non-canonical amino acid. Each of these two extra domains was effectively produced and functionalized with a variety of biological and chemical molecules. Structural properties of the resulting tripartite chimeric protein were investigated using molecular modelling approaches, and its potential for the multi-functionalization of cellulose was confirmed experimentally. As a proof of concept, we show that cellulose can be labelled with a fluorescent version of the tripartite protein grafted to magnetic beads and captured using a magnet.

International audience; Education of our intestinal immune system early in life strongly influences adult health. This education strongly relies on series of events that must occur in well-defined time windows. From initial colonization by maternal-derived microbiota during delivery to dietary changes from mother's milk to solid foods at weaning, these early-life events have indeed long-standing consequences on our immunity, facilitating tolerance to environmental exposures or, on the contrary, increasing the risk of developing noncommunicable diseases such as allergies, asthma, obesity, and inflammatory bowel diseases. In this review, we provide an outline of the recent advances in our understanding of these events and how they are mechanistically related to intestinal immunity development and education. First, we review the susceptibility of neonates to infections and inflammatory diseases, related to their immune system and microbiota changes. Then, we highlight the maternal factors involved in protection and education of the mucosal immune system of the offspring, the role of the microbiota, and the nature of neonatal immune system until weaning. We also present how the development of some immune responses is intertwined in temporal and spatial windows of opportunity. Finally, we discuss pending questions regarding the neonate particular immune status and the activation of the intestinal immune system at weaning.

Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients. Single-cell sequencing allows us to profile antibody repertoire features and identify expanded clonal lineages. Mammalian display screening is used to reveal that 43 antibodies (of 132 candidates) derived from expanded plasma cell lineages are specific to SARS-CoV-2 antigens, including antibodies with high affinity to the SARS-CoV-2 receptor-binding domain (RBD) that exhibit potent neutralization and broad binding to the RBD of SARS-CoV-2 variants (of concern/interest)., Cell Reports, 38 (3), ISSN:2666-3864, ISSN:2211-1247

Isolation and characterization of antibodies in COVID-19 patients has largely focused on memory B cells, however it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in controlling and resolving SARS-CoV-2 infection. To date there is little known about the specificity of plasma cells in COVID-19 patients. This is largely because plasma cells lack surface antibody expression, which complicates their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and high-throughput mammalian display screening to interrogate the specificity of plasma cells from 16 convalescent COVID-19 patients. Single-cell sequencing allows us to profile antibody repertoire features in these patients and identify highly expanded clonal lineages. Mammalian display screening is employed to reveal that 37 antibodies (out of 132 candidates) derived from expanded plasma cell clonal lineages are specific for SARS-CoV-2 antigens, including antibodies that target the receptor binding domain (RBD) with high affinity and exhibit potent neutralization of SARS-CoV-2.One Sentence SummarySingle-cell antibody repertoire sequencing and high-throughput screening identifies highly expanded plasma cells from convalescent COVID-19 patients that produce SARS-CoV-2-specific antibodies capable of potent neutralization.

Summary: The monocyte-derived phagocytes termed LysoDCs are hallmarks of Peyer’s patches, where their main function is to sample intestinal microorganisms. Here, we study their differentiation pathways in relation with their sampling, migratory, and T cell-priming abilities. Among four identified LysoDC differentiation stages displaying similar phagocytic activity, one is located in follicles, and the others reside in subepithelial domes (SED), where they proliferate and mature as they get closer to the epithelium. Mature LysoDCs but not macrophages express a gene set in common with conventional dendritic cells and prime naive helper T cells in vitro. At steady state, they do not migrate into naive T cell-enriched interfollicular regions (IFRs), but upon stimulation, they express the chemokine receptor CCR7 and migrate from SED to the IFR periphery, where they strongly interact with proliferative immune cells. Finally, we show that LysoDCs populate human Peyer’s patches, strengthening their interest as targets for modulating intestinal immunity. : Wagner et al. dissect the differentiation pathways of the Peyer’s patch monocyte-derived dendritic cells termed LysoDCs. They show that LysoDCs mature as they get closer to the epithelium. Mature LysoDCs migrate to the periphery of the T cell zone, where proliferation of immune cells occurs only when stimulated. Keywords: intestinal immunity, Peyer’s patches, phagocytes, dendritic cells, monocyte-derived cells, LysoDC, cell differentiation, single-cell RNA sequencing, antigen sampling, naive T cell priming

Beyond host genetics, the environment determines microbiota-immunity interactions. Most recent studies have focused on the interconnections between micronutrients, microbial and immune populations. However, the control of the gut oxidative stress and redox status has been neglected. Oxidative stress sensitive (Ox-S) prokaryotes include butyrate producers and minority mucosa-associated immunogenic symbionts, such as specific Lactobacillus strains, Bifidobacterium adolescentis, and segmented filamentous bacteria which exemplify the mucosal “minority report” paradigm. Butyrate, produced by Lachnospiraceae, Ruminococcaceae and Bacteroidetes, is the main microbiota-derived gut mucosal immunity regulator and the best functional marker of the healthy mature anaerobic gut microbiota (HMAGM). Oxidative stress during the “window of opportunity” around weaning is observed in severe acute malnutrition and results in Ox-S prokaryote depletion, HMAGM disruption, collapse of butyrate production and durable gut mucosal immunity alteration. High saturated-fat diet leads to oxidative stress, selection of oxidative stress-resistant (Ox-R) Lactobacillus reuteri strains in Peyer’s patches, secretion of pro-inflammatory cytokines, disruption of mucosal immune compartmentalization (leaky gut) and obesity. Beyond dietary micronutrient diversity and pathogen control, future research should focus on antioxidants, control of oxidative stress and Ox-S gut prokaryote preservation as new instrumental targets for maintenance of the gut microbiota-immunity symbiotic loop and prevention of malnutrition and obesity. Keywords: Mucosal immunity, Gut microbiota, Oxidative stress, Nutrition, Peyer’s patches

Introduction Nous decrivons une serie de dermatoses developpees a l’occasion du confinement (mars–avril 2020) lors de la premiere vague de l’epidemie COVID-19. Materiel et methodes Cas no 1 : homme de 59 ans, isolement social, exogenose. Ulcerations diffuses du siege, du scrotum et de la verge, hemorragiques, douloureuses. Contexte de station au sol prolongee et maceration. Carences vitaminiques multiples (B9, zinc, fer, vitamine C, PP, D). Propos incoherents. Decouverte d’une encephalopathie de Gayet–Wernicke associee a un syndrome de Korsakoff. Cas no 2 : femme de 78 ans, isolement social, denutrition, probable maltraitance domestique (mari). Impotence fonctionnelle totale depuis plusieurs mois. Adressee pour une volumineuse escarre sacree. Decouverte de fractures deplacees des deux cols femoraux, non consolidees, anciennes. Cas no 3 : femme de 62 ans, isolement social, denutrition severe. Majoration de sa consommation alcoolique (livraison a domicile). Prurit, bulles tendues sur l’ensemble du corps et ulcerations etendues, hemorragiques. Atteinte du visage et des muqueuses. Carences en vitamine PP, C, B9. Diagnostic retenu : pemphigoide bulleuse dans une forme « historique » sur terrain denutri, avec retard de prise en charge. Cas no 4 : femme de 48 ans, anorexique, isolement social. Majoration de la consommation d’alcool lors du confinement et « peur de faire ses courses ». Erytheme bien limite œdemateux du dos des pieds, du decollete et des avant-bras, douloureux, d’evolution peripherique bulleuse. Carences en vitamines PP, B1, B6, C. Nous retenons le diagnostic d’erytheme pellagroide. Regression sous renutrition. Discussion A cote des manifestations cutanees correlees a la maladie COVID-19 (urticaire, exantheme maculopapuleux, eruption vesiculeuse…), nous souhaitions attirer l’attention sur d’autres manifestations dermatologiques indirectement liees a la pandemie. Le premier confinement a notamment ete marque par une augmentation de la consommation d’alcool en population generale, surtout en cas de consommation reguliere prealable et de trouble psychiatrique. A cela s’ajoutait la peur de faire ses courses, modifiant les habitudes alimentaires et favorisant le comportement de « binge-eating » (ou en l’occurrence « drinking »). L’exogenose et la denutrition ont ete a l’origine des dermatoses carentielles des patients no 1 et 4. L’isolement social a restreint le champ des interactions, induisant un huis-clos mortifere pouvant mener a des situations de maltraitance (patiente no 2). L’ensemble de ces cas illustre les dommages collateraux de la pandemie COVID-19. L’isolement social et le retard de soins ont joue un role majeur, soit dans la survenue de la dermatose elle-meme (dermatoses carentielles), soit dans son evolution pejorative (pemphigoide bulleuse avec retard de prise en charge), aboutissant a des presentations cliniques « historiques ».

La Presse Medicale - In Press.Proof corrected by the author Available online since samedi 13 mai 2017

In mammals, macrophages (MF) are present in virtually all tissues where they serve many different functions linked primarily to the maintenance of homeostasis, innate defense against pathogens, tissue repair and metabolism. Although some of these functions appear common to all tissues, others are specific to the homing tissue. Thus, MF become adapted to perform particular functions in a given tissue. Accordingly, MF express common markers but also sets of tissue-specific markers linked to dedicated functions. One of the largest pool of MF in the body lines up the wall of the gut. Located in the small intestine, Peyer's patches (PP) are primary antigen sampling and mucosal immune response inductive sites. Surprisingly, although markers of intestinal MF, such as F4/80, have been identified more than 30 years ago, MF of PP escaped any kind of phenotypic description and remained ``unknown'' for decades. In absence of MF identification, the characterization of the PP mononuclear phagocyte system (MPS) functions has been impaired. However, taking into account that PP are privileged sites of entry for pathogens, it is important to understand how the latter are handled by and/or escape the PP MPS, especially MF, which role in killing invaders is well known. This review focuses on recent advances on the PP MPS, which have allowed, through new criteria of PP phagocyte subset identification, the characterization of PP MF origin, diversity, specificity, location and functions.

The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b + conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b + cDCs belong to a unique SIRPα + cDC subset. At steady state, cDCs and TIM-4 + macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4 ' macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8α + interfollicular cDC number, and (iii) activation of both CD11b + and CD8α + interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.

La accesibilidad y el creciente uso de tecnologías en el salón de clases han transformado las formas en que los estudiantes universitarios se involucran en su proceso de aprendizaje. En particular, el uso de la mensajería de texto se ha convertido en una forma de comunicación cotidiana entre jóvenes, al menos en ciertos sectores sociales, a través de todo el mundo. Con el interés de explorar la experiencia de esta práctica en el salón de clases, se creó el Cuestionario sobre Experiencia y Uso de la Mensajería de texto en el Salón de clase (CEUMS). El CEUMS fue administrado a una muestra de 238 estudiantes sub graduados del Departamento de Psicología de la Universidad de Puerto Rico (M=50; F=183; Otro=5). Los resultados indican que en promedio, un estudiante envía y recibe 19 mensajes de texto durante una clase de una hora y veinte minutos (enviados=9; recibidos=10) y que esta práctica se repite en al menos cuatro de cinco clases en las que se encuentran matriculados. Aunque no se encontró una relación significativa entre el uso de la mensajería de texto y el involucramiento en el aprendizaje (r = -.04 p>.05), los estudiantes reportan opiniones variadas sobre esta práctica, entre las que se incluyen: uso condicionado de la mensajería de texto en el salón de clase, la percepción de esta práctica como un distractor que afecta el aprendizaje y/o como una herramienta de aprendizaje para compartir información de la clase.

Enterococcus faecalis WHE 96, a strain isolated from soft cheese based on its anti- Listeria activity, produced a 5,494-Da bacteriocin that was purified to homogeneity by ultrafiltration and cation-exchange and reversed-phase chromatographies. The amino acid sequence of this bacteriocin, named enterocin 96, was determined by Edman degradation, and its structural gene was sequenced, revealing a double-glycine leader peptide. After a comparison with other bacteriocins, it was shown that enterocin 96 was a new class II bacteriocin that showed very little similarity with known structures. Enterocin 96 was indeed a new bacteriocin belonging to class II bacteriocins. The activity spectrum of enterocin 96 covered a wide range of bacteria, with strong activity against most gram-positive strains but very little or no activity against gram-negative strains.

Summary The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis., Graphical abstract, Highlights • Spatial proteogenomic single-cell atlas of healthy and obese murine and human liver • Validated flow cytometry and microscopy panels for all hepatic cells • LAMs are differentially located in the lean and obese liver • Evolutionary conserved BMP9/10-ALK1 axis is essential for KC development, By combining single-cell and -nucleus sequencing with spatial mapping of RNA and proteins, this vast spatial proteogenomic atlas of healthy and obese human and mouse livers presents methods to identify and localize all hepatic cells and provides insights into hepatic myeloid cells, including identification of reliable surface markers for isolation and localization of hepatic macrophages, characterization of lipid-associated macrophages in both healthy and steatotic livers, determination of a key regulatory axis of Kupffer cell development, and identification of a conserved core gene expression signature of Kupffer cells across 7 species, including chickens and zebrafish.