5 research outputs found
Study of autophagy during co-infection between Measles virus and Salmonella typhimurium
Le virus de la rougeole est un agent pathogĂšne responsable dâimmunosuppressions transitoires mais sĂ©vĂšres chez les individus infectĂ©s. Lâinfection par ce virus peut ainsi mener Ă lâĂ©tablissement dâinfections secondaires opportunistes, souvent dĂ©crites chez les patients rougeoleux. Cependant, la contribution du virus de la rougeole sur des infections secondaires Ă lâĂ©chelle de la cellule co-infectĂ©e nâa jamais fait lâobjet dâĂ©tudes. Notre Ă©quipe Ă prĂ©cĂ©demment dĂ©montrĂ© que le virus de la rougeole induit une autophagie productive dans les cellules infectĂ©es, requise pour une rĂ©plication optimale du virus. Ă lâopposĂ©, certains pathogĂšnes comme la bactĂ©rie Salmonella typhimurium sont restreints par lâautophagie. Le but de cette thĂšse est dâĂ©tudier la contribution de lâautophagie sur la prolifĂ©ration bactĂ©rienne en condition de co-infection avec le virus de la rougeole. Au cours du projet, nous avons identifiĂ© que dans les cellules co-infectĂ©es avec le virus de la rougeole, la bactĂ©rie Salmonella typhimurium hyperprolifĂšre. Cette prolifĂ©ration intense prend place essentiellement dans des cellules multinuclĂ©Ă©es gĂ©antes (syncytia) formĂ©es par le virus. En outre, la bactĂ©rie, normalement localisĂ©e dans une vacuole cellulaire, se localise dans le cytosol de ces syncytia et semble insensible Ă lâautophagie. Au cours de cette thĂšse, nous avons identifiĂ© que le facteur antimicrobien TBK1 pourrait ĂȘtre dĂ©tournĂ© par lâinfection virale, contribuant ainsi Ă lâĂ©chappement de la bactĂ©rie Ă lâautophagie. Ce travail de thĂšse met ainsi en Ă©vidence une nouvelle possibilitĂ© dâĂ©chappement de bactĂ©ries Ă lâautophagie lors dâune co-infection virale.Measles virus is a pathogenic agent responsible for transient but severe immunosuppression in infected individuals. The infection can lead to the establishment of secondary infections, frequently described in measles virus infected patients. Nevertheless, Measles virus contribution to secondary infection at cell scale level have never been studied yet. Our team has previously described that Measles virus induce a fully functional autophagy in infected cells, which is mandatory for an efficient viral replication. On the opposite, some pathogens, as the bacteria Salmonella typhimurium are restricted by autophagy. The aim of this PhD project is to study the contribution of autophagy on bacterial proliferation upon Measles virus co-infection at cell level. During this project, we have identified that in Measles virus coinfected cells, Salmonella typhimurium hyperproliferates. This exacerbated proliferation takes place in multinucleated giant cells induced by the virus, which are called syncytia. In addition, the bacteria, which is normally localized in cellular vacuole, is localized directly inside the cytosol of syncytia. Furthermore, cytosolic bacteria appears to be insensitive to autophagy. During this PhD project, we have identified that the cellular factor TBK1 could be hijack by the viral infection. Thus, this could allow the auophagic escape of the bacteria. This study highlight a new opportunity of autophagic escape of bacteria during a viral co-infection
Distinct Contributions of Autophagy Receptors in Measles Virus Replication
International audienceAutophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO_2 and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection
Measles Virus-Imposed Remodeling of the Autophagy Machinery Determines the Outcome of Bacterial Coinfection
International audienc
High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohnâs Disease
International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohnâs disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohnâs perianal disease followed up in the Cancers Et Surrisque AssociĂ© aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohnâs disease. Subjects were followed up for a median time of 35 months (interquartile range, 29â40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohnâs lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistulaârelated adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistulaârelated adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohnâs disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohnâs disease have a high risk of anal cancer, including perianal fistulaârelated cancer, and a high risk of rectal cancer