Unveiling the role of the immune checkpoint ligand CD200 in the host infection by Leishmania spp.

• Grant number: 20/13562-0
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2021 - November 30, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Mauro Javier Cortez Véliz
• Grantee: Mauro Javier Cortez Véliz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The immune checkpoint inhibitory mechanism mediated by the ligand CD200 and its receptor CD200R have been described to play a critical role in the host immune response, favoring Leishmania infection. While CD200R is mainly expressed in cells of the innate immune system such as macrophages, the ligand CD200 can occur in many different cell types. Our previous work has shown that macrophages express CD200 during infection by virulent protozoan parasites of the genus Leishmania. Moreover, the expression of CD200 can be induced by microvesicles released by the parasite inside the parasitophorous vacuole. The expression of CD200 in infected macrophages results in a self-inhibitory mechanism that impairs the microbicidal response mediated by iNOS/NO in favor of parasite resistance and proliferation. In this proposal, we aim to identify, characterize, and validate the importance of CD200/CD200R in the pathology and progression of different clinical manifestations of leishmaniasis in humans. Moreover, we will investigate the Leishmania microvesicles content involved in CD200 induction from infected macrophages, testing the top sequence candidates as potential CD200 agonists in murine models of Leishmania infection. Finally, we propose to extend our findings in tumor-bearing mice and evaluate the signaling pathways associated with CD200/CD200R by testing the top CD200 agonist candidates in a potential therapeutic approach in multiple clinical settings. (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)

CARVALHO, DANILO O.; COSTA-DA-SILVA, ANDRE L.; PETERSEN, VIVIAN; DE SOUZA, MICAEL SANTANA; IOSHINO, RAFAELLA S.; MARQUES, ISABEL C. S.; FRANZ, ALEXANDER W. E.; OLSON, KEN E.; JAMES, ANTHONY A.; CAPURRO, MARGARETH L.. Transgene-induced cell death following dengue-2 virus infection in Aedes aegypti. SCIENTIFIC REPORTS, v. 13, n. 1, p. 11-pg., 2023-04-12. (12/24105-3, 20/13562-0, 08/10254-1)

STAQUICINI, I, FERNANDA; HAJITOU, AMIN; DRIESSEN, WOUTER H. P.; PRONETH, BETTINA; CARDO-VILA, MARINA; STAQUICINI, I, DANIELA; MARKOSIAN, CHRISTOPHER; HOH, MARIA; CORTEZ, MAURO; HOODA-NEHRA, ANUPAMA; et al. Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer. eLIFE, v. 10, JUN 1 2021. (12/24105-3, 20/13562-0)

ORREGO, PATRICIO R.; SERRANO-RODRIGUEZ, MAYELA; CORTEZ, MAURO; ARAYA, JORGE E.. In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles. BIOMOLECULES, v. 11, n. 9, SEP 2021. (20/13562-0, 12/24105-3)