An innovative therapeutic educational program to support older drivers with cognitive disorders: Description of a randomized controlled trial study protocol

Older drivers face the prospect of having to adjust their driving habits because of health problems, which can include neurocognitive disorders. Self-awareness of driving difficulties and the interaction between individual with neurocognitive disorders and natural caregiver seem to be important levers for the implementation of adaptation strategies and for the subsequent voluntary cessation of driving when the cognitive disorders become too severe. This study aims to evaluate an educational program for patient/natural caregiver dyads who wish to implement self-regulation strategies in driving activity, and to improve self-awareness of driving ability. The ACCOMPAGNE program is based on seven group workshops, which target the dyad. The workshops deal with the impact of cognitive, sensory and iatrogenic disorders on driving. They tackle questions about responsibility, and about autonomy and social life. They also provide alternative solutions aimed at maintaining outward-looking activities even if driving is reduced or stopped. A randomized controlled trial is planned to evaluate the effectiveness of the program 2 months and 6 months after inclusion, and to compare this to the effectiveness of conventional approaches. The main outcome of this trial (i.e., the implementation of self-regulated driving strategies), will be measured based on scores on the “Current Self-Regulatory Practices” subscale of the Driver Perception and Practices Questionnaire. The Driving Habits Questionnaire will be used to measure secondary outcomes (indicators of driving changes; indicators of changes in mood, quality of life and caregiver burden; and self-awareness of driving abilities). Indicators will be collected for both patients and natural caregivers. This cognitive, social and psychological program should allow older individuals with cognitive disorders to drive more safely, and help to maintain the quality of life and mood of both patient and natural caregiver despite driving limitations. The patient's care path would be optimized, as he/she would become an actor in the process of giving up driving, which will, most certainly, be needed at some point in the progress of neurocognitive disorders. This process ranges from becoming aware of driving difficulties, to implementing self-regulation strategies, through to complete cessation of driving when necessary.Clinical trial registration numberNCT04493957

Simple, Rapid Mycobacterium ulcerans Disease Diagnosis from Clinical Samples by Fluorescence of Mycolactone on Thin Layer Chromatography

Introduction: Mycobacterium ulcerans infection, known as Buruli ulcer, is a disease of the skin and subcutaneous tissues which is an important but neglected tropical disease with its major impact in rural parts of West and Central Africa where facilities for diagnosis and management are poorly developed. We evaluated fluorescent thin layer chromatography (f-TLC) for detection of mycolactone in the laboratory using samples from patients with Buruli ulcer and patients with similar lesions that gave a negative result on PCR for the IS2404 repeat sequence of M. ulcerans Methodology/Principal findings Mycolactone and DNA extracts from fine needle aspiration (FNA), swabs and biopsy specimen were used to determine the sensitivity and specificity of f-TLC when compared with PCR for the IS2404. For 71 IS2404 PCR positive and 28 PCR negative samples the sensitivity was 73.2% and specificity of 85.7% for f-TLC. The sensitivity was similar for swabs (73%), FNAs (75%) and biopsies (70%). Conclusions: We have shown that mycolactone can be detected from M. ulcerans infected skin tissue by f-TLC technique. The technique is simple, easy to perform and read with minimal costs. In this study it was undertaken by a member of the group from each endemic country. It is a potentially implementable tool at the district level after evaluation in larger field studies

Community dialogue to enhance understanding of beliefs, behaviours and barriers to care for people living with liver disease and HBV infection in KwaZulu Natal, South Africa

INTRODUCTION: The World Health Organisation (WHO) has set targets for the elimination of Hepatitis B virus (HBV), which include preventing new infections and reducing deaths. We explored beliefs, behaviours and barriers to diagnosis, prevention and treatment for people living with HBV infection (PLWHB) and those with liver disease in a rural South African population in KwaZulu-Natal, to gather information to inform research and support the development of improved clinical and public health services. METHODS: Using an interdisciplinary approach (combining public engagement, social science, clinical and laboratory team members) we conducted a community dialogue with members of the Africa Health Research Institute (AHRI) Community Advisory Board (CAB). Notes from the discussions were used to write up an account from which themes were identified during a team debrief session for data analysis. RESULTS: There was a lack of knowledge and awareness of HBV infection and transmission and prevention amongst CAB members, also reported among community members and healthcare workers. The participants recognised liver disease symptoms. Perceived causes of liver disease reported by the CAB were alcohol and non-adherence to HIV treatment. Barriers to care included stigma, poverty, and delays in referrals for HBV diagnosis and management. CONCLUSION: Understanding barriers to care is important to shape future services for diagnosis, treatment and prevention of HBV and liver disease which are accessible, affordable and acceptable to the local population. Education, awareness and advocacy for improved liver health care pathways are required to make them effective for local communities

Evaluating the yaws diagnostic gap: A survey to determine the capacity of and barriers to improving diagnostics in all yaws-endemic countries

BACKGROUND: Yaws, caused by Treponema pallidum subsp. pertenue, is a skin neglected tropical disease. It is targeted for eradication by 2030, primarily using mass drug administration (MDA) with azithromycin. Traditionally, diagnosis of yaws has relied on clinical examination and serological testing. However, these approaches have poor diagnostic performance. To achieve eradication, more accurate diagnostics are required to determine whether MDA should be initiated or continued as well as for post-elimination surveillance. Molecular tools will be crucial for detecting antimicrobial resistant cases, which have the potential to derail eradication efforts. In order to determine the feasibility of introducing novel, more accurate, diagnostics for yaws surveillance purposes, it is necessary to understand current in-country diagnostic capacity. This study therefore aimed to understand the current capacity of, and challenges to, improving diagnostics for yaws in all yaws-endemic countries worldwide. METHODOLOGY/ PRINCIPLE FINDINGS: An online survey was sent to all 15 yaws-endemic countries in July 2021. The survey asked about past prevalence estimates, the availability of different diagnostic tools, and perceived barriers to enhancing capacity. Fourteen countries responded to the survey, four of which did not have a current National Policy for yaws eradication in place. Over 95% of reported that yaws cases from the past five years had not been confirmed with serological or molecular tools, largely due to the limited supply of rapid serological tests. Only four countries reported having operational laboratories for molecular yaws diagnosis, with only one of these having a validated assay to detect azithromycin resistance. CONCLUSIONS AND SIGNIFICANCE: This study highlights the diagnostic capacity constraints across all respondent countries. Countries are in need of access to a sustainable supply of serological tests, and development of molecular testing facilities. Sufficient sustainable funding should be made available to ensure that appropriate diagnostic tools are available and utilised

La polarisation des macrophages hépatique par HBsAg comme moyen de maintenance virale

Les macrophages hépatiques sont impliqués à la fois dans des mécanismes de tolérances et de clairances des pathogènes. Afin de mieux comprendre leur rôle dans les infections chroniques du Virus de l’Hépatite B (VHB) et de l’Hépatite Delta (VHD), nous avons caractérisé phénotypiquement l’interaction existant in vivo et ex vivo entre le VHB et macrophages primaires humains (MPH) ou des monocytes primaires, différentiés en macrophages pro- ou anti-inflammatoires (M1-MDMs ou M2-MDMs respectivement). Les MPH ou MDMs ont été exposé à différents génotypes du VHB et leur activation a été étudié par ELISA ou RT-qPCR. Des biopsies hépatiques de patient chroniquement infectés par le VHB ont été analysé par RT-qPCR ou immunohistochimie. Les paramètres viraux du VHB et VHD dans des Hépatocytes Primaires Humains (HPH) et des HepaRG différentiées ont été suivi par ELISA, qPCR ou RT-qPCR. Dans des biopsies hépatiques de patients VHB, nous avons montré la présence de la protéine de capside du VHB (HBc) au contact des macrophages, associé à une augmentation des marques anti-inflammatoires de ces derniers. L’exposition ex vivo de PLMs au VHB entraine une diminution de leurs sécrétions de cytokines pro-inflammatoires. L’incubation de MDMs avec le VHB de génotype C et D entraine une diminution des sécrétions pro-inflammatoires des M1-MDMs (IL-6 et IL-1β) ainsi qu’une augmentation des cytokines anti-inflammatoires chez les M2-MDMs exposés au VHB-B, C et D. Des expériences de cocultures nous ont par la suite permis d’identifier la protéine d’enveloppe du VHB (HBsAg) comme étant la principale actrice des modulations observées. Le VHB et le VHD partageant la même protéine d’enveloppe, des modifications similaires sont observées en présence de virions de VHD. Aussi, nous avons montré que les cytokines produites par les M1-MDMs sont capable de diminuer l’établissement de l’infection VHB dans les hépatocytes, mais pas celles qui sont produites par des M1-MDMs exposés au VHB. De plus, une forte diminution dose dépendante de la maintenance des ARNs du VHB (génotype A à E) ainsi que du VHD a été observé dans des hépatocytes infectés, suite à un traitement avec de l’IL-1β recombinante. Cette inhibition semble dépendante de l’activation de la voie NFkB et impliquer, au moins en partie, la déstabilisation des ARNs viraux. En conclusion, nos données suggèrent que le VHB module les fonctions des macrophages hépatiques pour favoriser son établissement et sa persistance.Liver macrophages can be both involved in pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macrophages (PLM) and primary blood monocytes differentiated into pro-inflammatory or anti-inflammatory macrophages (M1-MDM or M2-MDM, respectively). PLM or primary blood monocytes either ex-vivo differentiated into M1-MDM or M2-MDM were exposed to HBV from different genotype and their activation followed by ELISA or RT-qPCR. Liver biopsies from HBV infected patients were analysed by RT-qPCR or immunohistochemistry. Viral parameters in HBV-infected primary human hepatocytes (PHH) and differentiated HepaRG cells were followed by ELISA, qPCR and RT-qPCR analyses. We evidenced the presence of HBc protein within macrophages in liver biopsies from HBV-infected patients and higher levels of anti-inflammatory macrophages markers, compared to non-infected ones. Ex vivo exposure of naive PLM to HBV led to a reduced secretion of pro-inflammatory cytokines. Upon exposure to HBV (from genotype C and D) during differentiation and activation, M1-MDM secreted less IL-6 and IL-1β, whereas M2-MDM secreted more IL-10 when exposed to HBV (from genotype B, C or D) during activation. Using a co-culture approach, we identified HBV envelope particle (HBsAg) as being responsible for the aforementioned modulations of M1-MDMs. As expected, HDV virions, which also display HBsAg, behaved similarly. We also showed that cytokines produced by M1-MDM, but not those produced by HBV-exposed M1-MDM, decreased HBV establishment in hepatocytes. Besides, we observed a strong dose-dependent decrease of HBV RNAs (from genotypes A to E) and HDV RNAs maintenance upon treatment of infected hepatocytes with recombinant IL-1β. This inhibition was shown to be dependent on the activation of the NFkB pathway and would at least involved mechanism targeting HBV RNAs stability. Altogether, our data strongly suggest that HBV modulates liver macrophage functions to favor its establishment and persistence

La polarisation des macrophages hépatique par HBsAg comme moyen de maintenance virale

Liver macrophages can be both involved in pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macrophages (PLM) and primary blood monocytes differentiated into pro-inflammatory or anti-inflammatory macrophages (M1-MDM or M2-MDM, respectively). PLM or primary blood monocytes either ex-vivo differentiated into M1-MDM or M2-MDM were exposed to HBV from different genotype and their activation followed by ELISA or RT-qPCR. Liver biopsies from HBV infected patients were analysed by RT-qPCR or immunohistochemistry. Viral parameters in HBV-infected primary human hepatocytes (PHH) and differentiated HepaRG cells were followed by ELISA, qPCR and RT-qPCR analyses. We evidenced the presence of HBc protein within macrophages in liver biopsies from HBV-infected patients and higher levels of anti-inflammatory macrophages markers, compared to non-infected ones. Ex vivo exposure of naive PLM to HBV led to a reduced secretion of pro-inflammatory cytokines. Upon exposure to HBV (from genotype C and D) during differentiation and activation, M1-MDM secreted less IL-6 and IL-1β, whereas M2-MDM secreted more IL-10 when exposed to HBV (from genotype B, C or D) during activation. Using a co-culture approach, we identified HBV envelope particle (HBsAg) as being responsible for the aforementioned modulations of M1-MDMs. As expected, HDV virions, which also display HBsAg, behaved similarly. We also showed that cytokines produced by M1-MDM, but not those produced by HBV-exposed M1-MDM, decreased HBV establishment in hepatocytes. Besides, we observed a strong dose-dependent decrease of HBV RNAs (from genotypes A to E) and HDV RNAs maintenance upon treatment of infected hepatocytes with recombinant IL-1β. This inhibition was shown to be dependent on the activation of the NFkB pathway and would at least involved mechanism targeting HBV RNAs stability. Altogether, our data strongly suggest that HBV modulates liver macrophage functions to favor its establishment and persistence.Les macrophages hépatiques sont impliqués à la fois dans des mécanismes de tolérances et de clairances des pathogènes. Afin de mieux comprendre leur rôle dans les infections chroniques du Virus de l’Hépatite B (VHB) et de l’Hépatite Delta (VHD), nous avons caractérisé phénotypiquement l’interaction existant in vivo et ex vivo entre le VHB et macrophages primaires humains (MPH) ou des monocytes primaires, différentiés en macrophages pro- ou anti-inflammatoires (M1-MDMs ou M2-MDMs respectivement). Les MPH ou MDMs ont été exposé à différents génotypes du VHB et leur activation a été étudié par ELISA ou RT-qPCR. Des biopsies hépatiques de patient chroniquement infectés par le VHB ont été analysé par RT-qPCR ou immunohistochimie. Les paramètres viraux du VHB et VHD dans des Hépatocytes Primaires Humains (HPH) et des HepaRG différentiées ont été suivi par ELISA, qPCR ou RT-qPCR. Dans des biopsies hépatiques de patients VHB, nous avons montré la présence de la protéine de capside du VHB (HBc) au contact des macrophages, associé à une augmentation des marques anti-inflammatoires de ces derniers. L’exposition ex vivo de PLMs au VHB entraine une diminution de leurs sécrétions de cytokines pro-inflammatoires. L’incubation de MDMs avec le VHB de génotype C et D entraine une diminution des sécrétions pro-inflammatoires des M1-MDMs (IL-6 et IL-1β) ainsi qu’une augmentation des cytokines anti-inflammatoires chez les M2-MDMs exposés au VHB-B, C et D. Des expériences de cocultures nous ont par la suite permis d’identifier la protéine d’enveloppe du VHB (HBsAg) comme étant la principale actrice des modulations observées. Le VHB et le VHD partageant la même protéine d’enveloppe, des modifications similaires sont observées en présence de virions de VHD. Aussi, nous avons montré que les cytokines produites par les M1-MDMs sont capable de diminuer l’établissement de l’infection VHB dans les hépatocytes, mais pas celles qui sont produites par des M1-MDMs exposés au VHB. De plus, une forte diminution dose dépendante de la maintenance des ARNs du VHB (génotype A à E) ainsi que du VHD a été observé dans des hépatocytes infectés, suite à un traitement avec de l’IL-1β recombinante. Cette inhibition semble dépendante de l’activation de la voie NFkB et impliquer, au moins en partie, la déstabilisation des ARNs viraux. En conclusion, nos données suggèrent que le VHB module les fonctions des macrophages hépatiques pour favoriser son établissement et sa persistance

La polarisation des macrophages hépatique par HBsAg comme moyen de maintenance virale

Liver macrophages can be both involved in pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macrophages (PLM) and primary blood monocytes differentiated into pro-inflammatory or anti-inflammatory macrophages (M1-MDM or M2-MDM, respectively). PLM or primary blood monocytes either ex-vivo differentiated into M1-MDM or M2-MDM were exposed to HBV from different genotype and their activation followed by ELISA or RT-qPCR. Liver biopsies from HBV infected patients were analysed by RT-qPCR or immunohistochemistry. Viral parameters in HBV-infected primary human hepatocytes (PHH) and differentiated HepaRG cells were followed by ELISA, qPCR and RT-qPCR analyses. We evidenced the presence of HBc protein within macrophages in liver biopsies from HBV-infected patients and higher levels of anti-inflammatory macrophages markers, compared to non-infected ones. Ex vivo exposure of naive PLM to HBV led to a reduced secretion of pro-inflammatory cytokines. Upon exposure to HBV (from genotype C and D) during differentiation and activation, M1-MDM secreted less IL-6 and IL-1β, whereas M2-MDM secreted more IL-10 when exposed to HBV (from genotype B, C or D) during activation. Using a co-culture approach, we identified HBV envelope particle (HBsAg) as being responsible for the aforementioned modulations of M1-MDMs. As expected, HDV virions, which also display HBsAg, behaved similarly. We also showed that cytokines produced by M1-MDM, but not those produced by HBV-exposed M1-MDM, decreased HBV establishment in hepatocytes. Besides, we observed a strong dose-dependent decrease of HBV RNAs (from genotypes A to E) and HDV RNAs maintenance upon treatment of infected hepatocytes with recombinant IL-1β. This inhibition was shown to be dependent on the activation of the NFkB pathway and would at least involved mechanism targeting HBV RNAs stability. Altogether, our data strongly suggest that HBV modulates liver macrophage functions to favor its establishment and persistence.Les macrophages hépatiques sont impliqués à la fois dans des mécanismes de tolérances et de clairances des pathogènes. Afin de mieux comprendre leur rôle dans les infections chroniques du Virus de l’Hépatite B (VHB) et de l’Hépatite Delta (VHD), nous avons caractérisé phénotypiquement l’interaction existant in vivo et ex vivo entre le VHB et macrophages primaires humains (MPH) ou des monocytes primaires, différentiés en macrophages pro- ou anti-inflammatoires (M1-MDMs ou M2-MDMs respectivement). Les MPH ou MDMs ont été exposé à différents génotypes du VHB et leur activation a été étudié par ELISA ou RT-qPCR. Des biopsies hépatiques de patient chroniquement infectés par le VHB ont été analysé par RT-qPCR ou immunohistochimie. Les paramètres viraux du VHB et VHD dans des Hépatocytes Primaires Humains (HPH) et des HepaRG différentiées ont été suivi par ELISA, qPCR ou RT-qPCR. Dans des biopsies hépatiques de patients VHB, nous avons montré la présence de la protéine de capside du VHB (HBc) au contact des macrophages, associé à une augmentation des marques anti-inflammatoires de ces derniers. L’exposition ex vivo de PLMs au VHB entraine une diminution de leurs sécrétions de cytokines pro-inflammatoires. L’incubation de MDMs avec le VHB de génotype C et D entraine une diminution des sécrétions pro-inflammatoires des M1-MDMs (IL-6 et IL-1β) ainsi qu’une augmentation des cytokines anti-inflammatoires chez les M2-MDMs exposés au VHB-B, C et D. Des expériences de cocultures nous ont par la suite permis d’identifier la protéine d’enveloppe du VHB (HBsAg) comme étant la principale actrice des modulations observées. Le VHB et le VHD partageant la même protéine d’enveloppe, des modifications similaires sont observées en présence de virions de VHD. Aussi, nous avons montré que les cytokines produites par les M1-MDMs sont capable de diminuer l’établissement de l’infection VHB dans les hépatocytes, mais pas celles qui sont produites par des M1-MDMs exposés au VHB. De plus, une forte diminution dose dépendante de la maintenance des ARNs du VHB (génotype A à E) ainsi que du VHD a été observé dans des hépatocytes infectés, suite à un traitement avec de l’IL-1β recombinante. Cette inhibition semble dépendante de l’activation de la voie NFkB et impliquer, au moins en partie, la déstabilisation des ARNs viraux. En conclusion, nos données suggèrent que le VHB module les fonctions des macrophages hépatiques pour favoriser son établissement et sa persistance

La polarisation des macrophages hépatique par HBsAg comme moyen de maintenance virale

Liver macrophages can be both involved in pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macrophages (PLM) and primary blood monocytes differentiated into pro-inflammatory or anti-inflammatory macrophages (M1-MDM or M2-MDM, respectively). PLM or primary blood monocytes either ex-vivo differentiated into M1-MDM or M2-MDM were exposed to HBV from different genotype and their activation followed by ELISA or RT-qPCR. Liver biopsies from HBV infected patients were analysed by RT-qPCR or immunohistochemistry. Viral parameters in HBV-infected primary human hepatocytes (PHH) and differentiated HepaRG cells were followed by ELISA, qPCR and RT-qPCR analyses. We evidenced the presence of HBc protein within macrophages in liver biopsies from HBV-infected patients and higher levels of anti-inflammatory macrophages markers, compared to non-infected ones. Ex vivo exposure of naive PLM to HBV led to a reduced secretion of pro-inflammatory cytokines. Upon exposure to HBV (from genotype C and D) during differentiation and activation, M1-MDM secreted less IL-6 and IL-1β, whereas M2-MDM secreted more IL-10 when exposed to HBV (from genotype B, C or D) during activation. Using a co-culture approach, we identified HBV envelope particle (HBsAg) as being responsible for the aforementioned modulations of M1-MDMs. As expected, HDV virions, which also display HBsAg, behaved similarly. We also showed that cytokines produced by M1-MDM, but not those produced by HBV-exposed M1-MDM, decreased HBV establishment in hepatocytes. Besides, we observed a strong dose-dependent decrease of HBV RNAs (from genotypes A to E) and HDV RNAs maintenance upon treatment of infected hepatocytes with recombinant IL-1β. This inhibition was shown to be dependent on the activation of the NFkB pathway and would at least involved mechanism targeting HBV RNAs stability. Altogether, our data strongly suggest that HBV modulates liver macrophage functions to favor its establishment and persistence.Les macrophages hépatiques sont impliqués à la fois dans des mécanismes de tolérances et de clairances des pathogènes. Afin de mieux comprendre leur rôle dans les infections chroniques du Virus de l’Hépatite B (VHB) et de l’Hépatite Delta (VHD), nous avons caractérisé phénotypiquement l’interaction existant in vivo et ex vivo entre le VHB et macrophages primaires humains (MPH) ou des monocytes primaires, différentiés en macrophages pro- ou anti-inflammatoires (M1-MDMs ou M2-MDMs respectivement). Les MPH ou MDMs ont été exposé à différents génotypes du VHB et leur activation a été étudié par ELISA ou RT-qPCR. Des biopsies hépatiques de patient chroniquement infectés par le VHB ont été analysé par RT-qPCR ou immunohistochimie. Les paramètres viraux du VHB et VHD dans des Hépatocytes Primaires Humains (HPH) et des HepaRG différentiées ont été suivi par ELISA, qPCR ou RT-qPCR. Dans des biopsies hépatiques de patients VHB, nous avons montré la présence de la protéine de capside du VHB (HBc) au contact des macrophages, associé à une augmentation des marques anti-inflammatoires de ces derniers. L’exposition ex vivo de PLMs au VHB entraine une diminution de leurs sécrétions de cytokines pro-inflammatoires. L’incubation de MDMs avec le VHB de génotype C et D entraine une diminution des sécrétions pro-inflammatoires des M1-MDMs (IL-6 et IL-1β) ainsi qu’une augmentation des cytokines anti-inflammatoires chez les M2-MDMs exposés au VHB-B, C et D. Des expériences de cocultures nous ont par la suite permis d’identifier la protéine d’enveloppe du VHB (HBsAg) comme étant la principale actrice des modulations observées. Le VHB et le VHD partageant la même protéine d’enveloppe, des modifications similaires sont observées en présence de virions de VHD. Aussi, nous avons montré que les cytokines produites par les M1-MDMs sont capable de diminuer l’établissement de l’infection VHB dans les hépatocytes, mais pas celles qui sont produites par des M1-MDMs exposés au VHB. De plus, une forte diminution dose dépendante de la maintenance des ARNs du VHB (génotype A à E) ainsi que du VHD a été observé dans des hépatocytes infectés, suite à un traitement avec de l’IL-1β recombinante. Cette inhibition semble dépendante de l’activation de la voie NFkB et impliquer, au moins en partie, la déstabilisation des ARNs viraux. En conclusion, nos données suggèrent que le VHB module les fonctions des macrophages hépatiques pour favoriser son établissement et sa persistance

How to get away with liver innate immunity? A viruses’ tale

International audienceIn their never-ending quest towards persistence within their host, hepatitis viruses have developed numerous ways to counteract the liver innate immunity. This review highlights the different and common mechanisms employed by these viruses to (i) establish in the liver (passive entry or active evasion from immune recognition) and (ii) actively inhibit the innate immune response (ie modulation of pattern recognition receptor expression and/or signalling pathways, modulation of interferon response and modulation of immune cells count or phenotype)

Inhibitory Effect of IL-1β on HBV and HDV Replication and HBs Antigen-Dependent Modulation of Its Secretion by Macrophages

International audienceCo-infection with the hepatitis B virus and hepatitis delta virus (HDV) leads to the most aggressive form of viral hepatitis. Using in vitro infection models, we confirmed that IL-1β, a crucial innate immune molecule for pathogen control, was very potent against HBV from different genotypes. Additionally, we demonstrated for the first time a strong and rapid antiviral effect induced by very low doses of IL-1β against HDV. In parallel, using co-culture assays, we demonstrated that monocytes exposed to HBV, and in particular to HBsAg, during differentiation into pro-inflammatory macrophages secreted less IL-1β. Altogether, our data emphasize the importance of developing combined antiviral strategies that would, for instance, reduce the secretion of HBsAg and stimulate the immune system to produce endogenous IL-1β efficient against both HBV and HDV