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Bouchery T.,CNRS Laboratory of Communication Molecules and Adaptation of Microorganisms
Parasite (Paris, France) | Year: 2012

Filariases are caused by onchocercid nematodes that are transmitted by arthropod vectors. More than 180 million people are infected worldwide. Mass drug administration has been set up in many endemic areas to control the parasite burden. Although very successful in limiting microfilarial load, transmission has not been completely interrupted in such areas. A proportion of infected patients with lymphatic filariasis or loiasis are known to be amicrofilaremic, as they do not present microfilariae in their bloodstream despite the presence of adult worms. A mirror status also exists in CBA/Ca mice infected with Litomosoides sigmodontis, the well-established model of filariasis. Using this model, the goal of this study was to determine if the kinetics of blood clearance of microfilariae differed between amicrofilaremic CBA/Ca mice and microfilaremic BALB/c mice. For this purpose, a qPCR approach was devised to detect microfilariae in different tissues, after a controlled inoculation of microfilariae. We showed that the rapid clearance of microfilariae from the pleural cavity or from the bloodstream of CBA/Ca mice was associated with a massive accumulation of first stage larvae in the lungs, liver and spleen. Source

Bodo B.,CNRS Laboratory of Communication Molecules and Adaptation of Microorganisms
Actualite Chimique | Year: 2015

From the middle of the XVIIIth century, when chemists and doctors began to take interest in the composition of gallstones and the time when the cholesterol structure was established rigorously, two centuries have passed. The chemist Chevreul had a crucial contribution firstly for the clarification he has made on the nature of animal fat and on the saponification reaction from the distinction he made between saponifiable and unsaponifiable compounds. He isolated and characterized cholesterol from gallstones and published his results in 1815. The Chevreul's sample of cholesterol conserved in the laboratory of chemistry of the Muséum was pure, as we have checked it by modern spectral analysis. Cholesterol is certainly the molecule which has involved for his knowledge as many chemists and Nobel laureates in chemistry and medicine Award, and its right chemical structure including the absolute configuration of its chiral centres was only known in the middle of the XXth century. It is also probably one of the most familiar chemical compounds for the general public. It is this long chemical history that is presented here with its key stakeholders. Source

Dubar F.,CNRS Laboratory of Catalysis and Solid State Chemistry | Slomianny C.,French Institute of Health and Medical Research | Khalife J.,French Institute of Health and Medical Research | Dive D.,French Institute of Health and Medical Research | And 4 more authors.
Angewandte Chemie - International Edition | Year: 2013

Metal health: Ferroquine is a ferrocene-based analogue of the antimalarial drug chloroquine. In addition to the primary mechanism of quinoline action, fluorescent probe studies in infected red blood cells show another mechanism is at work. It is based on the production of HO. in the acidic and oxidizing environment of the digestive vacuole of the malaria parasite and implies that, with ferroquine, reinvasion can be inhibited. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Li Y.,Helmholtz Center for Infection Research | Li Y.,CNRS Laboratory of Communication Molecules and Adaptation of Microorganisms | Luxenburger E.,Helmholtz Center for Infection Research | Muller R.,Helmholtz Center for Infection Research
Angewandte Chemie - International Edition | Year: 2013

Take a detour: An alternative pathway to synthesize isovaleryl coenzyme A (CoA) has recently been suggested in myxobacteria, which is highly active when leucine is limited. Each enzymatic step of this unprecedented route has now been characterized and a novel 3-methylglutaconyl CoA decarboxylase identified that has apparently evolved from CoA transferases. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Bouchery T.,CNRS Laboratory of Communication Molecules and Adaptation of Microorganisms
PloS one | Year: 2012

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms. Source

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