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

Author(s)

Melo, Guilherme D. ; Goyard, Sophie ; Fiette, Laurence ; Boissonnas, Alexandre ; Combadiere, Christophe ; Machado, Gisele F. ; Minoprio, Paola ; Lang, Thierry

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, AUG 16 2017.
• Web of Science Citations: 6

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 Ly6C(high) macrophages in an environment presenting a variety of pro-inflammatory mediators (IFN-gamma, IL-1 beta, 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-1 beta, TNF-alpha 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. (AU)

• FAPESP's process: 14/03078-3 - Neuropathogenesis of experimental visceral leishmaniasis: investigation of parasite migration and immune response in a murine model
• Grantee: Guilherme Dias de Melo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate