Learning Tolerance while Fighting Ignorance

Research on microbe-host interactions focuses principally on pathogens, yet our immune system must deal with the huge number of beneficial commensal bacteria in our gut. It is becoming clear that the host immune system must reach a delicate balance between destroying dangerous bacterial pathogens while preserving the beneficial gut microbiota

Microbiologie et maladies infectieuses

Enseignement Cours et séminaires – Symbiose, antibiose, eubiose, dysbiose : quand les bactéries osent Le cours 2017-2018 a été un point d’étape important dans un domaine extrêmement dynamique de la microbiologie : le microbiote. L’objectif était une mise à jour sur des sujets clés : les mécanismes assurant stabilité, robustesse et résilience du microbiote intestinal ainsi que les mécanismes sous-tendant son effet de barrière contre des microbes intrus, en particulier pathogènes ; les bases et..

Shigellosis: An Old Disease in New Clothes?

Sansonetti discusses a "landmark" study of the epidemiology of shigellosis, involving over 600,000 people of all ages in six Asian countries

Tracking bacterial pathogens with genetically-encoded reporters

AbstractDuring the infectious process, bacterial pathogens are subject to changes in environmental conditions such as nutrient availability, immune response challenges, bacterial density and physical contacts with targeted host cells. These conditions occur in the colonized organs, in diverse regions within infected tissues or even at the subcellular level for intracellular pathogens. Integration of environmental cues leads to measurable biological responses in the bacterium required for adaptation. Recent progress in technology enabled the study of bacterial adaptation in situ using genetically encoded reporters that allow single cell analysis or whole body imaging based on fluorescent proteins, alternative fluorescent assays or luciferases. This review presents a historical perspective and technical details on the methods used to develop transcriptional reporters, protein–protein interaction assays and secretion detection assays to study pathogenic bacteria adaptation in situ. Finally, studies published in the last 5years on gram positive and gram negative bacterial adaptation to the host during infection are discussed. However, the methods described here could easily be extended to study complex microbial communities within host tissue and in the environment

Innate immune receptor NOD2 mediates LGR5+ intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation

International audienceThe nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist muramyl dipeptide (MDP), a peptidoglycan motif common to all bacteria, supports leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)+ intestinal stem cell (ISC) survival through NOD2 activation upon an otherwise lethal oxidative stress-mediated signal. However, the underlying protective mechanisms remain unknown. Here, using irradiation as stressor and primarily murine-derived intestinal organoids as a model system, we show that MDP induced a significant reduction of total and mitochondrial reactive oxygen species (ROS) within ISCs, which was associated with mitophagy induction. ATG16L1 knockout (KO) and NOD2 KO organoids did not benefit from the MDP-induced cytoprotection. We confirmed the MDP-dependent induction of ISC mitophagy upon stress in vivo. These findings elucidate the NOD2-mediated mechanism of cytoprotection involving the clearance of the lethal excess of ROS molecules through mitophagy, triggered by the coordinated activation of NOD2 and ATG16L1 by a nuclear factor κB (NF-κB)-independent pathway

The Galactic Isotropic γ\gamma-ray Background and Implications for Dark Matter

We present an analysis of the radial angular profile of the galacto-isotropic (GI) $\gamma$-ray flux--the statistically uniform flux in circular annuli about the Galactic center. Two different approaches are used to measure the GI flux profile in 85 months of Fermi-LAT data: the BDS statistic method which identifies spatial correlations, and a new Poisson ordered-pixel method which identifies non-Poisson contributions. Both methods produce similar GI flux profiles. The GI flux profile is well-described by an existing model of bremsstrahlung, $\pi^0$ production, inverse Compton scattering, and the isotropic background. Discrepancies with data in our full-sky model are not present in the GI component, and are therefore due to mis-modeling of the non-GI emission. Dark matter annihilation constraints based solely on the observed GI profile are close to the thermal WIMP cross section below 100 GeV, for fixed models of the dark matter density profile and astrophysical $\gamma$-ray foregrounds. Refined measurements of the GI profile are expected to improve these constraints by a factor of a few.Comment: 20 pages, 15 figures, references adde