Implications of Leishmania braziliensis prostaglandin F2-alpha synthase expression in the infection profile in mice

• Grant number: 13/22223-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 01, 2014
• End date: June 30, 2014
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Eliza Vanessa Carneiro Alves Ferreira
• Supervisor: Paul Martin Kaye
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of York, England
• Associated to the scholarship: 11/02040-4 - The role of Prostaglandin F2-alpha synthase in the interaction of Leishmania braziliensis with the mammalian host, BP.DR

Abstract

Leishmania Viannia braziliensis is the major ethiological agent of cutaneous leishmaniasis in Brazil and the species associated with the mucosal form of the disease which affects about 5% of patients and leads to progressive destruction of mucosal, cartilage or bones of the face, pharynx and larynx. Working with two paired mucosal (LbrM) and cutaneous (LbrC) L. braziliensis isolates, we detected, by proteome comparative analysis, a consistent differential pattern of expression of prostaglandin f2-alpha synthase (LbrPGF2S), which was upregulated in LbrC isolates when compared to LbrM isolates. Additionally, in silico analysis using the TritrypDB and TDR Targets Database showed that LbrPGF2S has been identified in the secretome of L. (V.) braziliensis, in the exosome of L. (L.) donovani and that it has a high potential as a drug target. We generated transfectants of L. braziliensis overexpressing LbrPGF2S that displayed a higher survival rate within the macrophage when compared to a control transfectant. To further investigate the LbrPGF2S role in host-parasite interaction we intend to thoroughly analyze host response to the parasites presenting different levels of the protein. Besides the LbrPGF2S overexpressor transfectant we will generate LbrPGF2S -/- or LbrPGF2S+/- parasites. Mice will be infected with L. braziliensis LbrPGF2S mutants and wild type cells; we will analyze disease progression and immune response to infection for one month, through the investigation of recruited cells and parasite distribution in the infection site by 2-photon intravital microscopy and dosage of cytokines released in infection site. (AU)