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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, AUG 16 2017.
• Citações Web of Science: 6

Resumo

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)

• Processo FAPESP: 14/03078-3 - Neuropatogenia da leishmaniose visceral experimental: investigação da migração parasitária e resposta imune em modelo murino
• Beneficiário: Guilherme Dias de Melo
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado