Alcool et tabac pendant la grossesse (conséquences pour le fœtus et mise en place d'un outil d'information à l'officine)

Bien que les principaux effets nocifs de l'alcool et du tabac soient en général connus du grand public, les dangers de ces drogues légales pendant la grossesse restent encore aujourd'hui mal identifiés par une grande partie de la population mais aussi par certains professionnels de santé. Une consommation d'alcool pendant la grossesse peut être responsable d'un ensemble plus ou moins complet d'anomalies malformatives et dysmorphiques, d'un retard de croissance et de troubles graves du développement neurologique, cognitif et comportemental. La fumée de tabac contient plusieurs milliers de substances chimiques, toxiques à la fois pour la femme enceinte, le fœtus et le nourrisson; la substance la plus dangereuse pour le foetus étant le monoxyde de carbone. Le tabagisme augmente le risque de complications pendant la grossesse, de mort fœtale in utero, de retard de croissance fœtale, d'accouchements prématurés et de mort subite du nourrisson. La grossesse représente un moment privilégié, au cours duquel les professionnels de santé ont l'occasion d'aider et d'accompagner les femmes enceintes dans une démarche de sevrage de leur consommation à risque. Ils doivent également mener des actions de prévention, notamment auprès des jeunes, de manière à relayer la campagne d'information Zéro alcool et zéro tabac pendant la grossesseLYON1-BU Santé (693882101) / SudocSudocFranceF

New chimeric TLR7/NOD2 agonist is a potent adjuvant to induce mucosal immune responses

International audienceBackground: PRR (Pattern Recognition Receptor) agonists have been widely tested as potent vaccine adjuvants. TLR7 (Toll-Like Receptor 7) and NOD2 (nucleotide-binding oligomerization domain 2) are key innate receptors widely expressed at mucosal levels.Methods: Here, we evaluated the immunostimulatory properties of a novel hybrid chemical compound designed to stimulate both TLR7 and NOD2 receptors.Finding: The combined TLR7/NOD2 agonist showed increase efficacy than TLR7L or NOD2L agonists alone or combined in different in vitro models. Dual TLR7/NOD2 agonist efficiently stimulates TLR7 and NOD2, and promotes the maturation and reprogramming of human dendritic cells, as well as the secretion of pro-inflammatory or adaptive cytokines. This molecule also strongly induces autophagy in human cells which is a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. In vivo, TLR7/NOD2L agonist is a potent adjuvant after intranasal administration with NP-p24 HIV vaccine, inducing high-quality humoral and adaptive responses both in systemic and mucosal compartments. Use of TLR7/NOD2L adjuvant improves very significantly the protection of mice against an intranasal challenge with a vaccinia virus expressing the p24.Interpretation: Dual TLR7/NOD2L agonist is a very potent and versatile vaccine adjuvant and promote very efficiently both systemic and mucosal immunity

Impact of IgA isoforms on their ability to activate dendritic cells and to prime T cells

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Impact of IgA isoforms on their ability to activate dendritic cells and to prime T cells

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Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation

(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 103 plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC

Exploiting Natural Cross-reactivity between Human Immunodeficiency Virus (HIV)-1 p17 Protein and Anti-gp41 2F5 Antibody to Induce HIV-1 Neutralizing Responses In Vivo

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First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations.

International audienceMucosal HIV-1-specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir

A high mucosal blocking score is associated with HIV protection

International audienceBACKGROUND:Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as α4β7 and the C-type lectins DC-SIGN and langerin. Previously Env-specific B-cell responses have been reported in highly exposed seronegative individuals (HESN).METHOD:Here, we studied gp120-specific antibodies ability to block HIV interaction with α4β7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to α4β7, DC-SIGN and/or langerin are induced in HESN. A mucosal blocking score (MBS) was defined based on the ability of antibodies to interfere with gp120/α4β7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV+ patients or HIV- unexposed healthy individuals.RESULTS:Antibodies reducing gp120 binding to both α4β7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV+ patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of α4β7 CD4+ T cells with primary isolates.CONCLUSIONS:MBS is significantly associated with protection in HESN and might reflect altered HIV spreading to mucosal-associated lymphoid tissues

Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases

International audienceHuman secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse-transcytosis, the apical-to-basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan-glycan interaction. Here, we asked whether IgA1 and IgA2-microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC-purified IgA, we show that reverse-transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA-bound microbiota in CD and UC showed distinct IgA1- and IgA2-associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti-glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis