Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice

Abstract : Visceral leishmaniasis (VL) is a systemic disease with multifaceted clinical manifestations, including neurological signs, however, the involvement of the nervous system during VL is underestimated. Accordingly, we investigated both brain infection and inflammation in a mouse model of VL. Using bioluminescent Leishmania donovani and real-time 2D-3D imaging tools, we strikingly detected live parasites in the brain, where we observed a compartmentalized dual-phased inflammation pattern: an early phase during the first two weeks post-infection, with the prompt arrival of neutrophils and Ly6Chigh macrophages in an environment presenting a variety of pro-inflammatory mediators (IFN-γ, IL-1β, CXCL-10/CXCR-3, CCL-7/CCR-2), but with an intense anti-inflammatory response, led by IL-10; and a re-inflammation phase three months later, extremely pro-inflammatory, with novel upregulation of mediators, including IL-1β, TNF-α and MMP-9. These new data give support and corroborate previous studies connecting human and canine VL with neuroinflammation and blood-brain barrier disruption, and conclusively place the brain among the organs affected by this parasite. Altogether, our results provide convincing evidences that Leishmania donovani indeed infects and inflames the brain.
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Scientific Reports, Nature Publishing Group, 2017, 7, pp.8454. 〈10.1038/s41598-017-09085-5〉
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Guilherme D. Melo, Sophie Goyard, Laurence Fiette, Alexandre Boissonnas, Christophe Combadiere, et al.. Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice. Scientific Reports, Nature Publishing Group, 2017, 7, pp.8454. 〈10.1038/s41598-017-09085-5〉. 〈hal-01581802〉

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