Institut des Sciences Sociales du Politique, French National Centre for Scientific Research

The effectiveness of intramuscular vaccines aimed at preventing severe COVID-19 remains limited due to waning immunity and the emergence of novel variants. Next-generation vaccines are needed for broader protection and blocking virus transmission. Here, we rationally designed an original nasal subunit vaccine composed of a fusion protein (SwFN) made of Wuhan spike and nucleoprotein combined with biocompatible mucosal nanocarriers (Nc). In mouse model, the nasal Nc-SwFN vaccine elicited multivalent serum and mucosal neutralizing antibodies. Robust spike and nucleoprotein cross-reactive immunity against variants was induced with a predominant phenotype of resident memory T cells in the lungs. Moreover, Nc-SwFN led to protective responses against Wuhan and Delta infection in relevant models with an absence of morbidity, mortality, and virus dissemination in the lungs and brain. Finally, Nc-SwFN drastically reduced host-to-host transmission. These promising results underscore the advantages of the nasal Nc-SwFN approach as a broad-spectrum vaccine candidate against current and emerging SARS-CoV-2 variants.

Super- and low-shedding phenomena have been observed in genetically homogeneous hosts infected by a single bacterial strain. To decipher the mechanisms underlying these phenotypes, we conducted an experiment with chicks infected with Salmonella Enteritidis in a non-sterile isolator, which prevents bacterial transmission between animals while allowing the development of the gut microbiota. We investigated the impact of four commensal bacteria called Mix4, inoculated at hatching, on chicken systemic immune response and intestinal microbiota composition and functions, before and after Salmonella infection. Our results revealed that these phenotypes were not linked to changes in cell invasion capacity of bacteria during infection. Mix4 inoculation had both short- and long-term effects on immune response and microbiota and promoted the low-shedder phenotype. Kinetic analysis revealed that Mix4 activated immune response from day 4, which modified the microbiota on day 6. This change promotes a more fermentative microbiota, using the aromatic compounds degradation pathway, which inhibited Salmonella colonization by day 11 and beyond. In contrast, control animals exhibited a delayed TNF-driven pro-inflammatory response and developed a microbiota using anaerobic respiration, which facilitates Salmonella colonization and growth. This strategy offers promising opportunities to strengthen the barrier effect against Salmonella and possibly other pathogens.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF. In newborn CF pigs, we observed changes in lung immune cell composition before the onset of infection that were dominated by increased monocyte infiltration, whereas neutrophil numbers remained constant. Flow cytometric and transcriptomic profiling revealed that the infiltrating myeloid cells displayed a more immature status. Cells with comparably immature transcriptomic profiles were enriched in the blood of CF pigs at birth as well as in preschool children with CF. This pattern coincided with decreased CD16 expression in the myeloid cells of both pigs and humans, which translated into lower phagocytic activity and reduced production of reactive oxygen species in both species. These results were indicative of a congenital, translationally conserved, and functionally relevant aberration of the immune system in CF. In newborn wild-type pigs, CFTR transcription in immune cells, including lung-derived and circulating monocytes, isolated from the bone marrow, thymus, spleen, and blood was below the detection limits of highly sensitive assays, suggesting an indirect etiology of the observed effects. Our findings highlight the need for additional immunological treatments to target innate immune deficits in patients with CF.

Influenza, a major “One Health” threat, has gained heightened attention following recent reports of highly pathogenic avian influenza in dairy cattle and cow-to-human transmission in the USA. This review explores general aspects of influenza A virus (IAV) biology, its interactions with mammalian hosts, and discusses the key considerations for developing vaccines to prevent or curtail IAV infection in the bovine mammary gland and its spread through milk

The task of legal precedent retrieval is essential yet challenging for legal professionals, as it involves identifying relevant past cases that can inform current legal decisions. Building on previous work that integrates citation networks and text similarity analysis, we apply these techniques to a dataset comprising paragraphs from cases decided by the Court of Justice of the European Union (CJEU). While paragraph citation retrieval is way more challenging than case citation retrieval, we show that a careful combination of network and text signals improves computational efficiency without sacrificing performances. More precisely, our experiments first reveal the limitations of network analysis at the paragraph level due to the sparse connectivity of the data. We then explore a novel approach to this task by combining network analysis at the case level and natural language processing at the paragraph level, which we refer to as “pincites”.

Mayotte is a small tropical island in the Comoros archipelago. It became recently a French department and much of its food, especially meat, is imported from abroad. The development of livestock farming is therefore a necessity. To understand the problems faced by Mahoran farmers, we organised semi-directive interviews with 15 farmers who reared cattle, sheep, goats or poultry. The first difficulty of farmers was limited access to land, especially for ruminants. This led to feed shortages. Another difficulty was the limited access to water and the poor quality of the roads to reach the farms. Poultry farmers were too dependent on importations of feed and laying hen or broiler genotypes from metropolitan France. The lack of organization for independent food productions (absence of abattoirs, cooperatives or organised markets) is also an obstacle to the development of the sector. Animal health, although not considered a major problem, has been a nuisance in the past (anthrax in cattle or salmonella in poultry). Mahoran farmers trust veterinarians or their assistants to manage health, although they complain about the high cost. Surprisingly, farmers use traditional medicine for many of their ailments, mostly based on local plants, but rarely for animals. Overall, our study reveals that larger land areas, better availability of money for investment and access to water and fodder are urgently required to improve livestock production and economic viability of farmers in Mayotte.

Both the quality of chicken meat and the quality of chicks are influenced by the level of breast muscle glycogen reserves. In order to study the role of digestive metabolism in establishing this muscular phenotype, we compared two divergent chicken lines for the ultimate pH (pHu) of the breast meat, a proxy for glycogen reserves. Males aged 4 weeks had twice the breast muscle glycogen content in the pHu- line (low pHu) than in the pHu + line (high pHu). The increase in glycogen reserves (pHu-) was associated with a higher relative weight of the proventriculus and gizzard, as well as better apparent ileal digestibility of nitrogen and calcium. The diversity of the cecal microbiota was comparable, but three bacterial genera (Lachnospira, Lachnospiraceae UCG-010, Caproiciproducens) varied between the lines. The differences observed could lead to down-regulation of carbon fixation in prokaryotes and of the citrate cycle in the pHu + line. RNA-seq analysis of the jejunum, the major site of nutrient absorption, revealed 149 genes differentially expressed (DE) between the lines, including several genes linked to immunity, hormonal response and circadian rhythms that are less expressed in pHu + animals. Others involved in cell migration and proliferation, and more generally tissue morphogenesis, also differed between the lines. Among the DE genes, several co-localized with Quantitative Trait Loci (QTL) controlling pHu and selection signatures identified in the divergent lines, such as the gene coding for ghrelin, a hormone regulating appetite.

Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1 ⁺ neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1 ⁻ counterpart. VRI-induced regulatory PD-L1 ⁺ neutrophils were generated remotely in the bone marrow in an IFN-γ–dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation, and reduced expression of resolving factors. These findings suggest that PD-L1 ⁺ neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.

Stressed bacteria can enter a dormant viable but non-culturable (VBNC) state. VBNC pathogens pose an increased health risk as they are undetectable by growth-based techniques and can wake up back into a virulent state. Although widespread in bacteria, the mechanisms governing this phenotypic switch remain elusive. Here, we investigate the VBNC state transition in the human pathogen Listeria monocytogenes. We show that bacteria starved in mineral water become VBNC by converting into osmotically stable cell wall-deficient coccoid forms, a phenomenon that occurs in other Listeria species. We reveal the bacterial stress response regulator SigB and the autolysin NamA as major actors of VBNC state transition. We lastly show that VBNC Listeria revert to a walled and virulent state after passage in chicken embryos. Our study provides more detail on the VBNC state transition mechanisms, revealing wall-free bacteria naturally arising in aquatic environments as a potential survival strategy in hypoosmotic and oligotrophic conditions.

Background Dairy cattle breeds are populations of limited effective size, subject to recurrent outbreaks of recessive defects that are commonly studied using positional cloning. However, this strategy, based on the observation of animals with characteristic features, may overlook a number of conditions, such as immune or metabolic genetic disorders, which may be confused with pathologies of environmental etiology. Results We present a data mining framework specifically designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. Conclusions The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

Mastitis is a major issue for the dairy industry. Despite multiple attempts, the efficacy of available mastitis vaccines is limited and this has been attributed to their incapacity to trigger robust cell-mediated immunity. Yeasts have recently been identified as promising antigen vectors capable of inducing T-cell responses, surpassing the antibody-biased mechanisms elicited by conventional adjuvanted vaccines. In this study, we combine in vitro, ex vivo, and in vivo approaches to evaluate the potential of the yeast Saccharomyces cerevisiae as a platform for novel vaccines against bovine mastitis. We demonstrate that S. cerevisiae is safe for intramuscular and intra-mammary immunisation in dairy cows. Vaccination resulted in a significant increase of IFNγ and IL-17 responses against the yeast platform but not against the vaccine antigen. These observations highlight that strategies to counterbalance the immunodominance of S. cerevisiae antigens are necessary for the development of successful vaccine candidates.

The gut microbiota exerts profound influence on poultry immunity and metabolism through mechanisms that yet need to be elucidated. Here we used conventional and germ-free chickens to explore the influence of the gut microbiota on transcriptomic and metabolic signatures along the gut-lung axis in poultry. Our results demonstrated a differential regulation of certain metabolites and genes associated with innate immunity and metabolism in peripheral tissues of germ-free birds. Furthermore, we evidenced the gut microbiota’s capacity to regulate mucosal immunity in the chicken lung during avian influenza virus infection. Finally, by fine-analysing the antiviral pathways triggered by the short-chain fatty acid (SCFA) butyrate in chicken respiratory epithelial cells, we found that it regulates interferon-stimulated genes (ISGs), notably OASL, via the transcription factor Sp1. These findings emphasize the pivotal role of the gut microbiota and its metabolites in shaping homeostasis and immunity in poultry, offering crucial insights into the mechanisms governing the communication between the gut and lungs in birds.

We identified and characterized genomic regions of Streptococcus agalactiae that are involved in the Leloir and the tagatose-6-phosphate pathways for D-galactose catabolism. The accumulation of mutations in genes coding the Leloir pathway and the absence of these genes in a significant proportion of the strains suggest that this pathway may no longer be necessary for S. agalactiae and is heading toward extinction. In contrast, a genomic region containing genes coding for intermediates of the tagatose-6-phosphate pathway, a Gat family PTS transporter, and a DeoR/GlpR family regulator is present in the vast majority of strains. By deleting genes that code for intermediates of each of these two pathways in three selected strains, we demonstrated that the tagatose-6-phosphate pathway is their sole route for galactose catabolism. Furthermore, we showed that the Gat family PTS transporter acts as the primary importer of galactose in S. agalactiae. Finally, we proved that the DeoR/GlpR family regulator is a repressor of the tagatose-6-phosphate pathway and that galactose triggers the induction of this biochemical mechanism. IMPORTANCE S. agalactiae, a significant pathogen for both humans and animals, encounters galactose and galactosylated components within its various ecological niches. We highlighted the capability of this bacterium to metabolize D-galactose and showed the role of the tagatose-6-phosphate pathway and of a PTS importer in this biochemical process. Since S. agalactiae relies on carbohydrate fermentation for energy production, its ability to uptake and metabolize D-galactose could enhance its persistence and its competitiveness within the microbiome.

Background In a previous nationwide survey in the Lebanese broiler production, multidrug-resistant CTX-M-producing E. coli were found to carry the mobile colistin resistance gene mcr-1. Objectives To investigate the mobile genetic supports responsible for the spread of these resistance genes among E. coli in healthy broilers in Lebanon. Methods Thirty-three blaCTX-M and mcr-1 positive E. coli of various sequence types from 17 broilers farms were subjected to conjugation assays. Long-read sequencing (Oxford Nanopore Technologies) and hybrid assembly were performed to determine complete plasmid sequences and their phylogenetic diversity. Results Twenty-nine conjugative IncFII plasmids harboured the extended-spectrum β-lactamase genes blaCTX-M-3 (n = 25) or blaCTX-M-55 (n = 4). Highly related IncF2:A-:B-/blaCTX-M-3 plasmids differing only through IS-mediated genetic rearrangements in antibiotic resistance gene clusters were found in genetically diverse E. coli strains isolated from distant farms. The mobile colistin resistance genes mcr-1.1 and mcr-1.26 were carried by IncX4 and IncI2 plasmids. Worryingly, in one isolate, the ISEcp1-blaCTX-M-55 transposable unit was found integrated in a mcr-1.26-carrying IncX4 plasmid. Beside expanded cephalosporins and colistin resistances, all E. coli isolates were multidrug-resistant with different additional resistances against aminoglycosides, (fluoro)quinolones, fosfomycin, phenicols, sulphonamides, tetracycline and trimethoprim. Conclusions Closely related blaCTX-M-3/55-borne IncF2:A-:B- plasmids harbouring variable MDR regions and mcr-1 carrying IncX4 plasmids are widely disseminated in the E. coli population of healthy broilers in Lebanon. Further surveillance programmes of antimicrobial resistance and interventions to reduce the abusive use of medically important antibiotics are necessary to limit the spread of resistances in food-producing animals in Lebanon.

Horizontal gene transfer (HGT) favors the acquisition and spread of antimicrobial resistance (AMR) genes in Salmonella , making it a major public health concern. We performed a bibliometric analysis to provide the current landscape of HGT in research on Salmonella AMR and identify emerging trends and potential research directions for the future. Data were collected from the Web of Science Core Collection and limited to articles and reviews published between 1999 and 2024 in English. VOSviewer 1.6.19 and CiteSpace 6.2.R1 software were used to conduct bibliometric analysis and visualize co-occurring keywords. A total of 1,467 publications were retrieved for analysis. American researchers contributed the most articles ( n = 310). In the meantime, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement have the highest citation/publication rate of 85.6. Recent studies have focused on the application of whole genome sequencing (WGS), Salmonella quinolone and colistin resistance, and the biocontrol of Salmonella AMR. These findings provide new insights into the role of HGT and help identify new targets for controlling the spread of AMR in Salmonella populations.

The question I will explore in this chapter is the following: what is this process of memorialisation that begins as soon as the attack occurs? How does it work exactly? How can we grasp it sociologically? I will begin by specifying what I understand by ‘immediate memorialisation’ and distinguish the different forms it takes. I will then trace how we move from an immediate memorialisation to a longer-term memorialisation, and in what way the usual distinction between ‘individual’ and ‘collective’ memory does not seem relevant to grasp it. Indeed, this process actually articulates not two, but three levels, which I will illustrate with examples from my research on the various attacks that have struck major European cities since 2001. Finally, I will conclude by showing how this way of conceiving the memorialisation of past attacks helps to better understand the way we react to new attacks.

Despite the success of mitigation policies in several countries to reduce the use of antibiotics in veterinary medicine, pathogenic and commensal bacteria resistant to antibiotics are still circulating in livestock animals. However, factors contributing the most to antimicrobial resistance (AMR) persistence in these settings are yet not clearly identified. The broiler production, with its highly segmented, pyramidal structure offers an ideal context to understand and control the spread of resistant bacteria. By taking advantage of an experimental facility reproducing the whole broiler production pyramid, we demonstrate that resistant E. coli persist in our system primarily though recirculation of a few commensal clones surviving in the rearing environment. No vertical transmission from hens to offspring nor strain acquisition at the hatchery were detected, while import of new strains from outside the facility seems limited. Moreover, each clone carries its own resistance-conferring plasmid(s), and a single putative plasmid horizontal transfer could have been inferred. These results, observed for now in a small experimental facility with high level of biosecurity, must be confirmed in a commercial farm context but still provide invaluable information for future mitigation policies.