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. U...

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Autores principales:	Guilherme D. Melo, Sophie Goyard, Laurence Fiette, Alexandre Boissonnas, Christophe Combadiere, Gisele F. Machado, Paola Minoprio, Thierry Lang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89cd1e4323e7400da7d481be4d8b9c5f
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spelling	oai:doaj.org-article:89cd1e4323e7400da7d481be4d8b9c5f2021-12-02T15:04:59ZUnveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice10.1038/s41598-017-09085-52045-2322https://doaj.org/article/89cd1e4323e7400da7d481be4d8b9c5f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09085-5https://doaj.org/toc/2045-2322Abstract 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.Guilherme D. MeloSophie GoyardLaurence FietteAlexandre BoissonnasChristophe CombadiereGisele F. MachadoPaola MinoprioThierry LangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guilherme D. Melo Sophie Goyard Laurence Fiette Alexandre Boissonnas Christophe Combadiere Gisele F. Machado Paola Minoprio Thierry Lang Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
description	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.
format	article
author	Guilherme D. Melo Sophie Goyard Laurence Fiette Alexandre Boissonnas Christophe Combadiere Gisele F. Machado Paola Minoprio Thierry Lang
author_facet	Guilherme D. Melo Sophie Goyard Laurence Fiette Alexandre Boissonnas Christophe Combadiere Gisele F. Machado Paola Minoprio Thierry Lang
author_sort	Guilherme D. Melo
title	Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
title_short	Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
title_full	Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
title_fullStr	Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
title_full_unstemmed	Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
title_sort	unveiling cerebral leishmaniasis: parasites and brain inflammation in leishmania donovani infected mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/89cd1e4323e7400da7d481be4d8b9c5f
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Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice

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