Crohn’s disease (CD) is a polygenic form of inflammatory bowel disease (IBD) that affects millions of individuals worldwide through the influence of environmental factors, such as tobacco smoking. The CD-associated inflammatory lesions have a tendency to develop where the bacterial load is the highest, while antibiotic treatment has long been used as unspecific therapy in some CD patients [1]. However, at present, the therapeutic management of CD is not curative and far from optimal. An overall of 25-30% of patients fail to respond to current biologics and/or to immunosuppressive drugs, resulting in accumulation of adverse events, including malignancies and serious infections. CD patients primarily experienced transmural inflammatory lesions at the terminal ileum, where Paneth cells are found more numerous. Importantly, Paneth cells showed abnormal granule formation, enhanced necroptosis and impaired secretion of antimicrobial peptides in CD [2]. By combining human genetic studies with animal model research, we and others have recently emphasized the pathophysiological role of Paneth cells in CD by identifying the major CD-predisposing NOD2 gene as a positive regulator of antimicrobial peptides secretion by Paneth cells in response to bacterial muramyl dipeptide [3, 4]. Consistently, genome-wide association studies revealed additional inborn errors in several regulatory factors involved in the maintenance of function of Paneth cells, arguing that a defective biology of secretory epithelial cells may lead to disease onset. Given that most current therapies for CD failed to modulate Paneth cells functionality [5], we now aim to select commensals that promote the antimicrobial response of Paneth cells. Our probiotic screening program identified that certain strains of probiotics triggered secretion of antimicrobial peptides by intestinal epithelial cells and of Th17-dependent signals that are thought to control innate antimicrobial immunity. More recently, we provided an explanation for the inefficiency of a selected Lactobacilli in clinical trials in CD by identifying that this probiotic strain improved disease severity in an experimental model of colitis through the CD-predisposing NOD2 gene [6]. Thanks to a national partnership between three academic institutions, a Foundation recognized as non-profit organization of public utility and a French industrial company, namely Bioprox, our project aims to select the most efficient combination of probiotic strains that can both exhibit anti-inflammatory potential and restore Paneth cell functionality. The BIOpaneX project is therefore focused on the further understanding of which and how certain anti-inflammatory symbionts may govern optimal Paneth cell secretion of antimicrobial peptides. Our specific goals are to i) identify which probiotics trigger Paneth cells-derived antimicrobial response, ii) dissect how selected probiotics coordinate Paneth cells function and iii) identify anti-inflammatory probiotic strains in two novel and relevant spontaneous models of CD. These experimental models provide us with unique tools to screen for more efficient probiotics leading to more rational therapies that do not depend on the major CD-predisposing NOD2 gene. That knowledge will not only advance our understanding of the biology of Paneth cells, but will also provide new therapies for physicians aimed at restoring topically defective antimicrobial immunity in CD. References: 1 Asquith M, Powrie F. J Exp Med 2010;207:1573-7. 2 Chamaillard M, Dessein R. World J Gastroenterol 2011;17:567-71. 3 Chamaillard M, Philpott D, Girardin SE, et al. Proc Natl Acad Sci U S A 2003;100:3455-60. 4 Kobayashi KS, Chamaillard M, Ogura Y, et al. Science 2005;307:731-4. 5 Kubler I, Koslowski MJ, Gersemann M, et al. Influence Aliment Pharmacol Ther 2009;30:621-33.

Current knowledge regarding the level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is mainly based on mathematical modeling, and most reports describing the prevalence of the infection are focused on inpatients and/or hospital health care workers (HCWs). However, to our knowledge, no such data have been reported from primary HCWs (PHCWs) despite them being at the frontline with coronavirus disease 2019 (COVID-19) patients. In this context, there is an urgent need to understand the extent of the infection and the level of immunity among PHCWs. In agreement with the COVID-19 research priorities identified by the World Health Organization and the research topics targeted by this ANR Recherche-Action COVID-19 call, we propose here a study aiming to describe the seroprevalence of immunoglobulin G (IgG) antibodies to SARS-CoV-2 among primary care physicians (general practitioners and pediatricians), pharmacists, and dentists. The seroprevalence among household contacts of seropositive and seronegative PHCWs will also be investigated. This research will be conducted based on four ongoing networks (French Sentinelles network, the IQVIA network, The French Association of Ambulatory Pediatrics [AFPA] network, and the Clinical Research in Liberal Dentistry [RECOL] network), which will allow us rapidly to include a representative sample of general practitioners, pediatricians, pharmacists, and dentists. We will conduct a cross-sectional study among PHCWs first, then among household contacts of seropositive and seronegative PHCWs. We will use an enzyme-linked immunosorbent assay (ELISA) designed for the detection of specific IgG antibodies to SARS-CoV-2 in humoral fluid, followed by a virus neutralization test to validate the ELISA results and estimate the levels of neutralizing antibodies. Clinical and epidemiological data will be collected through questionnaires, including sociodemographic information, health status, type of practice, adherence to infection prevention and control measures, risk behaviors, nonoccupational exposure to SARS-CoV-2, and household characteristics. First, we will assess the seroprevalence of IgG antibodies to SARS-CoV-2 among populations of PHCWs. Using the seroprevalence assessment methodology used by seroepidemiological studies carried out in the general population, such as the EpiCOV and Sapris, these results will be comparable to those of such seroepidemiological studies. Then, we will assess and compare the seroprevalence of IgG antibodies to SARS-CoV-2 among the household contacts of seropositive and seronegative PHCWs. We will also explore the short- and long-term clinical manifestations associated with SARS-CoV-2 infection. These data will allow a better understanding of SARS-CoV-2 infection and immunity levels among PHCWs and their household contacts and will provide essential knowledge for preparedness and response to contain COVID-19 to protect the frontline PHCWs.

The main objective of the project is the development of novel methods for the synthesis and functionalization of conductive nanocarbons for a new generation of field effect transistor sensors suitable for high sensitivity bio-sensing applications. This highly interdisciplinary research will be performed by 4 complementary laboratories: plasma-processing, nanomaterials, electronics, biology. Advanced carbons (carbon nanotubes, carbon-metal nanocomposites…) will be synthesized and primary functionalized by means of low temperature plasma-based techniques. Numerous in-situ diagnostics of the plasma will be performed in combination with the surface analysis to understand and control the grafting of functional groups at carbon surfaces. This will enable the targeted coupling of antibodies/proteins important for development of sensors for the detection of allergens or allergy markers in biological fluids. The knowledge transfer is targeting the field of the technological/industrial applications of plasma discharges as well as the the material and sensor production.