Study of two molecules that potentially modulate the success of macrophage infection by Leishmania amazonensis

• Grant number: 11/12634-9
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2011
• End date: April 30, 2014
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Beatriz Simonsen Stolf
• Grantee: Beatriz Simonsen Stolf
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmaniasis affects 12 million people worldwide and two million new cases are reported every year. Leishmania L. amazonensis is an important ethiological agent of the tegumentary form of the disease in Brazil and is responsible for a wide range of clinical forms.In Leishmania life cycle, amastigote forms live and multiplicate inside macrophages from the vertebrate host and promastigote forms live inside the insect vector. Since the success of the infection and consequently the form and severity of the disease depend on host and parasite factors, this project aims to study two proteins potentially important for infection: one from the macrophage and the other from the parasite. We will study macrophage CD100, which reduces the expression of inflammatory cytokines in human monocytes and is induced by proinflammatory stimuli. Our aim is to evaluate if CD100 affects macrophage infectivity by Leishmania. The second objective of the project focuses on metacaspase, a parasite protein that affects the survival inside macrophages. Metacaspases (MCAs) are evolutive distant forms of metazoan caspases present in protozoans, plants and fungi, also related to apoptosis. Little is known about proteins that regulate MCA activity. We will employ Phage display technology to select for Leishmania L. amazonensis MCA ligands that will lead to information about the enzyme´s regulation and that may induce parasite apoptosis without affecting the host cell. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PENA, MAURICIO S.; CABRAL, GUILHERME C.; FOTORAN, WESLEY L.; PEREZ, KATIA R.; STOLF, BEATRIZ S.. Metacaspase-binding peptide inhibits heat shock-induced death in Leishmania (L.) amazonensis. CELL DEATH & DISEASE, v. 8, MAR 2017. (11/12634-9)

LUQUE, MARIA C. A.; GALUPPO, MARIANA K.; CAPELLI-PEIXOTO, JANAINA; STOLF, BEATRIZ S.. CD100 Effects in Macrophages and Its Roles in Atherosclerosis. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 5, SEP 28 2018. (11/12634-9)

GALUPPO, MARIANA K.; DE REZENDE, ELOIZA; FORTI, FABIO L.; CORTEZ, MAURO; CRUZ, MARIO C.; TEIXEIRA, ANDRE A.; GIORDANO, RICARDO J.; STOLF, BEATRIZ S.. CD100/Sema4D Increases Macrophage Infection by Leishmania (Leishmania) amazonensis in a CD72 Dependent Manner. FRONTIERS IN MICROBIOLOGY, v. 9, JUN 5 2018. (11/12634-9)