📇 Rhumatologue ·
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Auteur de référence en rhumatologie
47 articles scientifiques publiés — un praticien à la pointe de la recherche
✨ Génération du profil synthétique IA en cours…
Secteur de conventionnement non disponible (médecin hospitalier ou non présent dans l'Annuaire santé CNAM des libéraux conventionnés).
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Journal of hepatology · 2014
Infection and immunity · 2009
ABSTRACTThe pathogenesis of cryptococcosis, including the events leading to the production of meningoencephalitis, is still largely unknown. Evidence of a transcellular passage ofCryptococcus neoformansacross the blood-brain barrier (BBB) and subsequent BBB disruption exists, but the paracellular passage of free yeasts and the role of monocytes in yeast dissemination and brain invasion (Trojan horse method) remain uncertain. We used our model of disseminated cryptococcosis, in which crossing of the BBB starts 6 h after intravenous inoculation, to study paracellular passage of the BBB. We prepared bone marrow-derived monocytes (BMDM) infected in vitro withC. neoformans(BMDM yeasts) and free yeasts and measured fungal loads in tissues. (i) Spleen and lung CFU were >2-fold higher in mice treated with BMDM yeasts than in those treated with free yeasts for 1 and 24 h (P< 0.05), while brain CFU were increased (3.9 times) only at 24 h (P< 0.05). (ii) By comparing the kinetics of brain invasion in naïve mice and in mice with preestablished cryptococcosis, we found that CFU were lower in the latter case, except at 6 h, when CFU from mice inoculated with BMDM yeasts were comparable to those measured in naïve mice and 2.5-fold higher than those in mice with preestablished cryptococcosis who were inoculated with free yeasts. (iii) Late phagocyte depletion obtained by clodronate injection reduced disease severity and lowered the fungal burden by 40% in all organs studied. These results provide evidence for Trojan horse crossing of the BBB byC. neoformans, together with mechanisms involving free yeasts, and overall for a role of phagocytes in fungal dissemination.
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Revue neurologique · 2004 · English Abstract
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