Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection

Following productive, lytic infection in epithelia, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation. In order to better understand what triggers this lytic/latent decision in neurons, we set up an organotypic model based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive infection in the explants. By contrast, selective application of the virus to distal axons led to a largely nonproductive infection that was characterized by the poor expression of lytic genes and the presence of high levels of the 2.0-kb major latency-associated transcript (LAT) RNA. Treatment of the explants with the immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV-2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus-induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in the absence of de novo protein synthesis was dependent on the presence of functional tegument protein VP16 in HSV-1 helper virus particles. After the establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV helper virus. In conclusion, the site of entry appears to be a critical determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons

The PtdIns 3-Kinase/Akt Pathway Regulates Macrophage-Mediated ADCC against B Cell Lymphoma

Macrophages are important effectors in the clearance of antibody-coated tumor cells. However, the signaling pathways that regulate macrophage-induced ADCC are poorly defined. To understand the regulation of macrophage-mediated ADCC, we used human B cell lymphoma coated with Rituximab as the tumor target and murine macrophages primed with IFNγ as the effectors. Our data demonstrate that the PtdIns 3-kinase/Akt pathway is activated during macrophage-induced ADCC and that the inhibition of PtdIns 3-kinase results in the inhibition of macrophage-mediated cytotoxicity. Interestingly, downstream of PtdIns 3-kinase, expression of constitutively active Akt (Myr-Akt) in macrophages significantly enhanced their ability to mediate ADCC. Further analysis revealed that in this model, macrophage-mediated ADCC is dependent upon the release of nitric oxide (NO). However, the PtdIns 3-kinase/Akt pathway does not appear to regulate NO production. An examination of the role of the PtdIns 3-kinase/Akt pathway in regulating conjugate formation indicated that macrophages treated with an inhibitor of PtdIns 3-kinase fail to polarize the cytoskeleton at the synapse and show a significant reduction in the number of conjugates formed with tumor targets. Further, inhibition of PtdIns 3-kinase also reduced macrophage spreading on Rituximab-coated surfaces. On the other hand, Myr-Akt expressing macrophages displayed a significantly greater ability to form conjugates with tumor cells. Taken together, these findings illustrate that the PtdIns 3-kinase/Akt pathway plays a critical role in macrophage ADCC through its influence on conjugate formation between macrophages and antibody-coated tumor cells

Impact du dispositif Contrat Local de Santé sur la capacité d’action dans les champs de la prévention, de la promotion de la santé et de la santé environnement dans les Régions Bretagne et Pays de la Loire. Rapport final sur le 1er mandat CLS du Direes

Presented as a tool for reducing social and territorial inequalities in health, it would be wrong to summarise the potential of local health contracts (CLS) solely in terms of their work in coordinating actions carried out at local level. While the mobilisation of actors in a given area can be expected to increase efficiency through concerted action to avoid the deployment of redundant initiatives, the CLS must also be seen as a "health in all policies" mechanism that can involve actors outside the social and health field. The heterogeneity of the actors involved suggests that a CLS could thus provide answers to complex problems that cannot be solved by working in silos.This report, produced as part of the first part of the CLS mandate given by the Regional Health Agencies of Brittany and Pays de la Loire as a result of the inter-regional health research, evaluation and expertise system (Direes), had the general aim of providing a better understanding of the impact and added value in terms of health promotion and health-environment of the CLSs deployed in their territories.Présenté comme un outil de réduction des inégalités sociales et territoriales de santé, on aurait tort de résumer le potentiel des contrats locaux de santé (CLS) à leur seul travail de coordination des actions menées à l’échelon local. Si l’on peut effectivement attendre de la mobilisation des acteurs d’un territoire un gain d’efficience par un travail de concertation évitant le déploiement d’initiatives redondantes, il faut aussi voir le CLS comme un dispositif de « santé dans toutes les politiques » susceptible d’impliquer des acteurs hors du champ socio-sanitaire. L’hétérogénéité des acteurs impliqués suggère qu’un CLS pourrait ainsi apporter des éléments de réponse à des problèmes complexes insolubles par un travail en silo.Ce rapport, produit dans le cadre du premier volet du mandat CLS confié par les Agences Régionales de Santé de Bretagne et Pays de la Loire découlant du Dispositif inter-régional de recherche, d’évaluation et d’expertise en santé (Direes), avait pour visée générale d’offrir une meilleure appréhension de l’impact et de la plus-value en matière de promotion de la santé et de santé-environnement des CLS déployés sur leur territoire

How primary care and public health interact in local health contracts in France?

International audienceThe demographic and epidemiological changes orient health care services towards communities with a focus on prevention and health promotion. Moreover, in France, the rapid decline of General Practitioners affect access to care in certain areas. Thus, it has made a call for interaction of primary care (PC) services and public health which can be strengthened by the actions at the local level. In 2009, the local health contracts (Contract local de santé; CLS) were developed to foster collaborative actions on the social determinants of health and to improve access to care. Considering the critical contribution of PC in these issues, one may ask how CLS mobilized PC and facilitate linkages between actions oriented toward population and primary care.The objective of this ancillary study (part of the CloterreS project), is to explore how often and how CLS involve PC in access to care and public health related actions.A mixed-method study based on document analysis, with a random sample of 17 CLSs (N = 165) from all French regions, was developed. A quantitative analysis of the 440 forms identified in 17 CLS computed frequency of involvement of PC actors and/or PC organizations and a qualitative analysis defined typology of interactions.All CLS and 20.1% (n = 86) of the forms involved PC actors and 43.2% (n = 185) concerned access to care. Of the access to care forms, 35.7% (n = 66) concerned PC. The most common strategies related to actions on the health workforce and on planning of services. The role of primary care professionals was as the target of the action and rarely as leader and partner.PC, mostly GP’s involvement, had a big place and access to care was at the core of local health contracts. The impact of CLS as an instrument to invite interaction public health and healthcare at the local level should be further assessed

Convergence de la « taxe soda » vers les recommandations internationales : une analyse du contenu des médias français

International audienceContexte : En dix ans, la taxe soda est passée d’expérimentation à une mesure recommandée par l’OMS et adoptée dans plusieurs juridictions. En 2012, la France a été parmi les premiers pays à en faire usage, pour la modifier ensuite en 2018. La façon dont est présentée une politique influence son acceptabilité, sa conception, son évaluation. Dans le cadre d’un projet de recherche pluridisciplinaire (Soda-Tax), nous étudions l’évolution du « cadrage » de la taxe soda, à savoir la définition du problème et des objectifs qui lui sont associés, en regard des recommandations internationales.Méthode : À partir du moteur Europresse®, nous avons réalisé une recension systématique d’articles abordant la taxe soda dans 24 quotidiens nationaux, régionaux et titres spécialisés entre 2011 et 2020. Nous avons développé un guide de codage informé par la littérature sur les processus de changement de politique publique afin de caractériser ce corpus d’articles et les positions exprimées sur le sujet par divers acteurs.Résultats : 470 articles ont été retenus en lien avec trois « pics » correspondant à des événements repérés respectivement entre août et décembre 2011 (n=352), avril et août 2016 (n=39), et août et décembre 2017 (n=79). L’exploration de leur contenu indique un recentrage de la taxe soda sur ses objectifs de santé publique plutôt que sur des considérations budgétaires, avec l’intention de faire évoluer la qualité de l’offre de boissons et non seulement les comportements des consommateurs.Discussion : Notre étude offre un éclairage rare sur l’évolution d’une taxe soda vers les recommandations internationales. Cette convergence suggère une forme d’apprentissage lié à la politique au fil du temps. L’analyse quantitative à venir permettra de documenter la couverture et l’évolution des positions respectives de différents acteurs, l’importance relative du contexte politique, économique et sanitaire dans leurs motivations ainsi qu’une éventuelle influence internationale