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Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
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Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
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Journal Article
Unveiling Cerebral Leishmaniasis: parasites and brain inflammation in Leishmania donovani infected mice
2017
Overview
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 Ly6C
high
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/51
/ 14
/ 14/5
/ 14/63
/ 38/77
/ 38/90
/ 64/60
/ Animals
/ Central Nervous System Protozoal Infections - metabolism
/ Central Nervous System Protozoal Infections - parasitology
/ Female
/ Humanities and Social Sciences
/ IL-1β
/ Inflammation Mediators - metabolism
/ Leishmania donovani - genetics
/ Leishmania donovani - metabolism
/ Leishmania donovani - physiology
/ Leishmaniasis - parasitology
/ Leishmaniasis, Visceral - metabolism
/ Leishmaniasis, Visceral - parasitology
/ Luciferases, Firefly - genetics
/ Luciferases, Firefly - metabolism
/ Luminescent Measurements - methods
/ Rodents
/ Science
